Apoptosis via MedWorm.com MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Apoptosis' source. Mon, 06 Feb 2012 16:52:01 +0100 C/EBP-α ameliorates CCl4-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo http://www.medworm.com/index.php?rid=5664291&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F624868238h21g482%2F This study investigated whether C/EBP-α exerts different apoptotic effects on hepatocytes and HSCs in vitro and in vivo. An adenovirus vector-expressing C/EBP-α gene was constructed, and a rat hepatic stellate cell lines (HSC-T6) and hepatocytes were transfected. A CCl4-induced liver fibrosis model in mice was also utilized. C/EBP-α induced apoptosis in hepatocytes and HSCs, but a significant difference between these cell types was observed in vitro. The mitochondrial pathway was involved in the apoptotic process and was predominant in HSC-T6 apoptosis. In the CCl4-induced mice liver fibrosis model, the administration of Ad-C/EBP-α decreased extracellular matrix deposition, including collagen and hydroxyproline content, and γ-GT levels, a marker of liver damage, were reduced sign... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5664291 Fri, 03 Feb 2012 17:12:22 +0100 5664291 Mechanisms to prevent caspase activation in rotenone-induced dopaminergic neurodegeneration: role of ATP depletion and procaspase-9 degradation http://www.medworm.com/index.php?rid=5656516&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd627g4825r411538%2F Abstract  The evidence implicating a mode of cell death that either favors or argues against caspase-dependent apoptosis is available in studies that used experimental models of Parkinson’s disease. We sought to investigate the mechanisms by which release of cytochrome c is not linked to caspase activation during rotenone-induced dopaminergic (DA) neurodegeneration. Unlike caspase activation in 6-hydroxydopamine-treated cells, both MN9D DA neuronal cells and primary cultures of mesencephalic neurons showed no obvious signs of caspase activation upon exposure to rotenone. We found that intracellular levels of ATP significantly decreased at the early phase of neurodegeneration (<~24 h) and therefore external addition of ATP to the lysates obtained at this stage reco... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5656516 Tue, 31 Jan 2012 07:11:38 +0100 5656516 Protein kinase A signals apoptotic activation in glucose-deprived hepatocytes: participation of reactive oxygen species http://www.medworm.com/index.php?rid=5635465&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl623p53441303204%2F We presented additional evidence sustaining this model: First, glucose withdrawal led to a 95% increase in mitochondrial cAMP levels in cultured hepatocytes; second, activation of PKA significantly augmented hepatic mitochondrial ROS generation, whereas PKA inhibition elicited the opposite effect. Mitochondrial PKA signaling, previously proposed as an autonomic pathway adjusting respiration rate, emerges as a mechanism of controlling cell survival during glucose restriction. Content Type Journal ArticleCategory Original PaperPages 1-17DOI 10.1007/s10495-012-0697-2Authors Anabela C. Ferretti, Institute of Experimental Physiology, CONICET, School of Biochemical Sciences, University of Rosario, Suipacha 570, S2002LRK, Rosario, ArgentinaStella M. Mattaloni, Institute of Experimental ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5635465 Tue, 24 Jan 2012 07:15:46 +0100 5635465 ICB3E induces iNOS expression by ROS-dependent JNK and ERK activation for apoptosis of leukemic cells http://www.medworm.com/index.php?rid=5617049&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2q7612554946w44j%2F Abstract  The role of c-Jun N terminal Kinase (JNK) has been well documented in various cellular stresses where it leads to cell death. Similarly, extracellular signal-regulated kinase (ERK) which was identified as a signalling molecule for survival pathway has been shown recently to be involved in apoptosis also. Recently we reported that ICB3E, a synthetic analogue of Piper betle leaf-derived apoptosis-inducing agent hydroxychavicol (HCH), possesses anti-chronic myeloid leukemia (CML) acitivity in vitro and in vivo without insight on mechanism of action. Here we report that ICB3E is three to four times more potent than HCH in inducing apoptosis of leukemic cells without having appreciable effects on normal human peripheral blood mononuclear cells, mouse fibroblast cell lin... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5617049 Wed, 18 Jan 2012 06:49:15 +0100 5617049 Hepatitis B vaccine induces apoptotic death in Hepa1–6 cells http://www.medworm.com/index.php?rid=5617050&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fnt2195177t44421h%2F We report that hepatitis B vaccine exposure resulted in significant upregulation of the key genes encoding caspase 7, caspase 9, Inhibitor caspase-activated DNase (ICAD), Rho-associated coiled-coil containing protein kinase 1 (ROCK-1), and Apoptotic protease activating factor 1 (Apaf-1). Upregulation of cleaved caspase 3,7 were detected by western blot in addition to Apaf-1 and caspase 9 expressions argues that cell death takes place via the intrinsic apoptotic pathway in which release of cytochrome c from the mitochondria triggers the assembly of a caspase activation complex. We conclude that exposure of Hepa1–6 cells to a low dose of adjuvanted hepatitis B vaccine leads to loss of mitochondrial integrity, apoptosis induction, and cell death, apoptosis effect was observed also in ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5617050 Tue, 17 Jan 2012 07:10:56 +0100 5617050 Swelling rather than shrinkage precedes apoptosis in serum-deprived vascular smooth muscle cells http://www.medworm.com/index.php?rid=5617051&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd25j418577486233%2F In this study, we employed a time-lapse, dual-image surface reconstruction technique to assess the volume of single vascular smooth muscle cells transfected with E1A-adenoviral protein (E1A-VSMC) and undergoing rapid apoptosis in the absence of growth factors or in the presence of staurosporine. After 30- to 60-min lag-phase, serum-deprived E1A-VSMC volume was increased by ~40%, which preceded maximal increments of caspase-3 activity and chromatin cleavage. Swollen cells underwent rapid apoptotic collapse, documented by plasma membrane budding, and terminated in 10–15 min by the formation of numerous apoptotic bodies. Suppression of apoptosis by inhibition of Na+,K+-ATPase and activation of cAMP signalling with ouabain and forskolin, respectively, completely abolished the swell... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5617051 Tue, 17 Jan 2012 07:10:55 +0100 5617051 Caspase-3 feeds back on caspase-8, Bid and XIAP in type I Fas signaling in primary mouse hepatocytes http://www.medworm.com/index.php?rid=5604040&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm122541jn5q70333%2F Abstract  The TNF-R1 like receptor Fas is highly expressed on the plasma membrane of hepatocytes and plays an essential role in liver homeostasis. We recently showed that in collagen-cultured primary mouse hepatocytes, Fas stimulation triggers apoptosis via the so-called type I extrinsic signaling pathway. Central to this pathway is the direct caspase-8-mediated cleavage and activation of caspase-3 as compared to the type II pathway which first requires caspase-8-mediated Bid cleavage to trigger mitochondrial cytochrome c release for caspase-3 activation. Mathematical modeling can be used to understand complex signaling systems such as crosstalks and feedback or feedforward loops. A previously published model predicted a positive feedback loop between active caspases-3 and ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5604040 Fri, 13 Jan 2012 16:55:42 +0100 5604040 Apoptosis in extracorporeal preserved inguinal fat flaps of the rat http://www.medworm.com/index.php?rid=5576690&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5tl27v64761071r1%2F This study was designed to investigate the apoptotic pathways of fat tissue in a permanent perfusion bioreactor system with the Hannover preservation solution and the Eurocollins solution in fat flaps of rats. In Lewis rats, the inguinal adipofascial flaps were elevated bilaterally and placed in a bioreactor at 37°C. To detect caspases 3, 8, 9 and 12, immunofluorescence stains of fat tissue specimen were analysed at several time points after preservation of flaps were placed in Hannover solution and Eurocollins solution for 10 days. An additional visual assessment of viability by a calcein based life/dead test was performed. It revealed a superior viability of the adipose tissue preserved in Hannover solution. Immunofluorescence staining demonstrated that apoptotic pathways vi... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5576690 Thu, 05 Jan 2012 17:04:55 +0100 5576690 Erratum to: Autophagy precedes apoptosis during the remodeling of silkworm larval midgut http://www.medworm.com/index.php?rid=5576691&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F42p8530630350832%2F Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s10495-011-0693-yAuthors Eleonora Franzetti, Department of Biotechnology and Life Sciences, University of Insubria, Via J. H. Dunant, 3, 21100 Varese, ItalyZhi-Jun Huang, Laboratory of Insect Molecular Biology and Biotechnology, Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, TianHe, Wushan Street, Guangzhou, 510642 ChinaYan-Xia Shi, Laboratory of Insect Molecular Biology and Biotechnology, Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, TianHe, Wushan Street, Guangzhou, 510642 ChinaKun Xie, Laboratory of Insect Molecular Bio... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5576691 Thu, 05 Jan 2012 17:04:54 +0100 5576691 Targeting colorectal cancer stem cells with inducible caspase-9 http://www.medworm.com/index.php?rid=5576692&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu747676n01866831%2F Abstract  Colorectal cancer stem cells (CSCs) drive tumor growth and are suggested to initiate distant metastases. Moreover, colon CSCs are reportedly more resistant to conventional chemotherapy, which is in part due to upregulation of anti-apoptotic Bcl-2 family members. To determine whether we could circumvent this apoptotic blockade, we made use of an inducible active caspase-9 (iCasp9) construct to target CSCs. Dimerization of iCasp9 with AP20187 in HCT116 colorectal cancer cells resulted in massive and rapid induction of apoptosis. In contrast to fluorouracil (5-FU)-induced apoptosis, iCasp9-induced apoptosis was independent of the mitochondrial pathway as evidenced by Bax/Bak double deficient HCT116 cells. Dimerizer treatment of colon CSCs transduced with iCasp9 (CSC-... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5576692 Thu, 05 Jan 2012 17:04:53 +0100 5576692 Preferential involvement of mitochondria in Toll-like receptor 3 agonist-induced neuroblastoma cell apoptosis, but not in inhibition of cell growth http://www.medworm.com/index.php?rid=5542223&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp1641405k4652366%2F Abstract  Double-stranded RNA (dsRNA) can mediate its therapeutic effect through Toll-like receptor 3 (TLR3) expressed on tumor cells including neuroblastoma. We used synthetic dsRNA polyinosinic-polycytidylic acid [Poly(I:C)] as a TLR3 agonist to treat TLR3-expressing SK-N-AS neuroblatoma (NB) cells. We found up-regulation of endoplasmic reticulum (ER) stress proteins glucose-regulated protein 78 and inositol-requiring enzyme 1. Bafilomycin A1, an inhibitor of ER function, effectively blocked poly(I:C)-induced activation of caspase-8, -9, and -3, MnSOD and glutathione peroxidase 1 and reduced poly(I:C)-induced SK-N-AS apoptosis. Pan caspase inhibitor and inhibitor of caspase-9, but not of caspase-8, inhibited poly(I:C)-induced activated caspase-3 expression. Rho zero (ρ0)... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5542223 Tue, 20 Dec 2011 16:44:02 +0100 5542223 Different apoptotic responses of RA synoviocytes depending on different genotypes of the mdm2 SNPT309G http://www.medworm.com/index.php?rid=5542222&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F01m4856w4p553337%2F Abstract  Mdm2 is an ubiquitin ligase, which binds p53 and blocks its function as a transcription factor in the pathway of apoptosis. Recently we have showed that the SNP mdm2 T309G has a protective effect of the minor allele in rheumatoid arthritis (RA). However, a functional impact on apoptosis by the different genotypes of the mdm2 SNP has not been investigated. Genomic DNA was obtained from 49 cell lines of synoviocytes derived from 49 patients with RA, and the mdm2 SNP309 was genotyped by polymerase chain reaction and restriction enzyme analysis. Seven cell lines were identified as homozygous for TT (major allele of mdm2 SNP309), and four as homozygous for GG (minor allele). All 11 cell lines were stimulated with 5 ng/ml of TNF alpha and 2.5 ng/ml of Il-1beta.... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5542222 Tue, 20 Dec 2011 16:44:02 +0100 5542222 Higenamine reduces HMGB1 during hypoxia-induced brain injury by induction of heme oxygenase-1 through PI3K/Akt/Nrf-2 signal pathways http://www.medworm.com/index.php?rid=5533471&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F22075744222j3274%2F Abstract  Growing lines of evidence suggests that high mobility group box-1 (HMGB1) plays an important role for promoting inflammation and apoptosis in brain ischemia. Previously, we demonstrated that inducers of heme oxygenase-1 (HO-1) significantly reduce HMGB1 release in inflammatory conditions in vitro and in vivo. Thus, we tested our hypothesis that higenamine protects brain injury by inhibition of middle cerebral artery occlusion (MCAO)-mediated HMGB1 release in vivo, and glucose/glucose oxidase (GOX)-induced apoptosis in C6 cells in vitro due to HO-1 induction. Higenamine increased HO-1 expression in C6 cells in both hypoxia and normoxia, in which the former was much more significant than the latter. Higenamine increased Nrf-2 luciferase activity, translocated Nrf-2 ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5533471 Mon, 19 Dec 2011 16:50:59 +0100 5533471 Methylseleninic acid potentiates multiple types of cancer cells to ABT-737-induced apoptosis by targeting Mcl-1 and Bad http://www.medworm.com/index.php?rid=5520413&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa480438w62kv57pg%2F Abstract  ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins, holds great promise to complement current cancer therapies. However many types of solid cancer cells are resistant to ABT-737. One practical approach to improve its therapeutic efficacy is to combine with the agents that can overcome such resistance to restore the sensitivity. In the present study, a second-generation selenium compound methylseleninic acid (MSeA) synergistically sensitized MDA-MB-231 human breast cancer cells, HT-29 human colon cancer cells and DU145 human prostate cancer cells to apoptosis induction by ABT-737, as evidenced by greater than additive enhancement of Annexin V/FITC positive (apoptotic) cells and activation of multiple caspases and PARP cleavage. Mechanistic investiga... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5520413 Fri, 16 Dec 2011 16:54:34 +0100 5520413 Induction of autophagy in hepatocellular carcinoma cells by SB203580 requires activation of AMPK and DAPK but not p38 MAPK http://www.medworm.com/index.php?rid=5512432&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj1ht18024445lj26%2F Abstract  SB203580 is a well-known inhibitor of p38 mitogen-activated protein kinase (MAPK). However, it can suppress cell proliferation in a p38 MAPK independent manner. The inhibitory mechanism remains unknown. Here, we showed that SB203580 induced autophagy in human hepatocellular carcinoma (HCC) cells. SB203580 increased GFP-LC3-positive cells with GFP-LC3 dots, induced accumulation of autophagosomes, and elevated the levels of microtubule-associated protein light chain 3 and Beclin 1. It stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and p53, but inhibited the phosphorylation of death-associated protein kinase (DAPK). Inhibition of AMPK, p53, or DAPK attenuated SB203580-induced autophagy. AMPK activation appeared to predate th... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5512432 Wed, 14 Dec 2011 16:43:03 +0100 5512432 Neuroprotective effects of human mesenchymal stem cells on neural cultures exposed to 6-hydroxydopamine: implications for reparative therapy in Parkinson’s disease http://www.medworm.com/index.php?rid=5501132&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj068552h103x6223%2F Abstract  Stem cell (SC) transplantation represents a promising tool to treat neurodegenerative disorders, such as Parkinson’s disease (PD), but positive therapeutic outcomes require elucidation of the biological mechanisms involved. Therefore, we investigated human Mesenchymal SCs (hMSCs) ability to protect murine differentiated Neural SCs (mdNSCs) against the cytotoxic effects of 6-hydroxydopamine (6-OHDA) in a co-culture model mimicking the in vivo neurovascular niche. The internalization of 6-OHDA mainly relies on its uptake by the dopamine active transporter (DAT), but its toxicity could also involve other pathways. We demonstrated that mdNSCs consistently expressed DAT along the differentiative process. Exposure to 6-OHDA did not affect hMSCs, but induced DAT-indepe... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5501132 Fri, 09 Dec 2011 17:03:18 +0100 5501132 Caspase-8 isoform 6 promotes death effector filament formation independent of microtubules http://www.medworm.com/index.php?rid=5501133&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh26545jg72365wj0%2F Abstract  Caspase-8 can trigger cell death following prodomain-mediated recruitment to the ‘death-inducing signaling complex.’ The prodomain consists of two death effector domain (DED) motifs that undergo homotypic interactions within the cell. Aside from mediating recruitment of procaspase-8, the prodomains have also been implicated in regulating cell survival, proliferation, death, senescence, differentiation, and substrate attachment. Here, we perform the initial characterization of a novel isoform of caspase-8, designated caspase-8 isoform 6 (Casp-8.6), which encodes both prodomain DEDs followed by a unique C-terminal tail. Casp-8.6 is detected in cells of the hematopoietic compartment as well as several other tissues. When Casp-8.6 expression is reconstituted in ca... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5501133 Fri, 09 Dec 2011 17:03:17 +0100 5501133 RNase MC2: a new Momordica charantia ribonuclease that induces apoptosis in breast cancer cells associated with activation of MAPKs and induction of caspase pathways http://www.medworm.com/index.php?rid=5473669&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6u7454855w508887%2F In conclusion, RNase MC2 is a potential agent which can be exploited in the worldwide fight against breast cancer. Content Type Journal ArticleCategory Original PaperPages 1-11DOI 10.1007/s10495-011-0684-zAuthors Evandro Fei Fang, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong KongChris Zhi Yi Zhang, State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaWing Ping Fong, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, Hong KongTzi Bun Ng, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Journal ApoptosisOnline ISSN 1573-675XPrint ISSN 1360-8185 (Source: Apoptosis) Apoptosis journals http://www.medworm.com/rss/comments.php?id=5473669 Thu, 01 Dec 2011 19:28:51 +0100 5473669 Regulation by survivin of cancer cell death induced by F14512, a polyamine-containing inhibitor of DNA topoisomerase II http://www.medworm.com/index.php?rid=5473670&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd0ut198n1174514t%2F In this study, using mainly P388 leukemia cells, we showed that activation of the DNA damage response by F14512 did not induce immediate apoptosis but resulted in an early growth arrest. F14512-induced G2 arrest was accompanied by the appearance of a senescence-like phenotype (characterized by an increased β-galactosidase staining) with up-regulation of the cyclin-dependent kinase inhibitor p16, and cyclin D1. The early senescence-based cell cycle block was characterized by a marked increase of the level of the IAP protein survivin, but not cIAP2, in P388 cells as well as in three other leukemia and melanoma cell types. The Thr(34)-phosphorylated form of survivin was observed within 4 h after F14512 exposure. Inhibition of survivin by siRNA resulted in a switch from senescence-... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5473670 Wed, 30 Nov 2011 04:39:08 +0100 5473670 Autophagy precedes apoptosis during the remodeling of silkworm larval midgut http://www.medworm.com/index.php?rid=5473672&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl13vq607886t2835%2F In this study, we perform a cellular, biochemical and molecular analysis of the degeneration process that occurs in the larval midgut of Bombyx mori during larval–adult transformation, with the aim to analyze autophagy and apoptosis in cells that die under physiological conditions. We demonstrate that larval midgut degradation is due to the concerted action of the two mechanisms, which occur at different times and have different functions. Autophagy is activated from the wandering stage and reaches a high level of activity during the spinning and prepupal stages, as demonstrated by specific autophagic markers. Our data show that the process of autophagy can recycle molecules from the degenerating cells and supply nutrients to the animal during the non-feeding period. Apoptosis inte... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5473672 Wed, 30 Nov 2011 04:39:07 +0100 5473672 Ras signaling contributes to survival of human T-cell leukemia/lymphoma virus type 1 (HTLV-1) Tax-positive T-cells http://www.medworm.com/index.php?rid=5473671&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fvl54gqh16j01l546%2F In this study we report data indicating that the apoptotic resistance of cells expressing Tax, constitutively or transiently, is linked to the intracellular levels of Ras-GTP. Indeed, we found that Tax-positive cells have a high content of active Ras, and that inhibition of Ras signaling, using the antagonist farnesyl thyosalicylic acid (FTS), increases their sensitivity to apoptosis. FTS treatment was also accompanied by a decrease in ERK, but not Akt, phosphorylation. Thus, all together our data suggest that the interaction between Tax and Ras could be important to ATLL pathogenesis, and indicate Ras as a possible target for therapeutic intervention in ATLL patients. Content Type Journal ArticleCategory Original PaperPages 1-10DOI 10.1007/s10495-011-0676-zAuthors Giovanna Sto... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5473671 Wed, 30 Nov 2011 04:39:07 +0100 5473671 Overexpression of microRNA-378 attenuates ischemia-induced apoptosis by inhibiting caspase-3 expression in cardiac myocytes http://www.medworm.com/index.php?rid=5465219&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0885l685x65q0267%2F This study first showed that miR-378 inhibited caspase-3 expression and attenuated ischemic injury in cardiomyocytes. It may represent a potential novel treatment for apoptosis and ischemic heart disease. Content Type Journal ArticleCategory Original PaperPages 1-14DOI 10.1007/s10495-011-0683-0Authors Ji Fang, Department of Physiology and the Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, 800 Xiangyin Road, Shanghai, 200433 People’s Republic of ChinaXiao-Wei Song, Department of Physiology and the Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, 800 Xiangyin Road, Shanghai, 200433 People’s Republic of ChinaJing Tian, Department of Physiology and the Key Laboratory of Mol... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5465219 Sat, 26 Nov 2011 16:46:25 +0100 5465219 Peptide-binding GRP78 protects neurons from hypoxia-induced apoptosis http://www.medworm.com/index.php?rid=5454088&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F175763793j468n74%2F This study is the first report on hypoxic neuronal and astrocyte cell surface GRP78 and suggests a potential therapeutic target for neuroprotection. Content Type Journal ArticleCategory Original PaperPages 1-11DOI 10.1007/s10495-011-0678-xAuthors Nitza Goldenberg-Cohen, Eye Research Laboratory, Felsenstein Medical Research Center, Tel-Aviv University, School of Medicine, Rabin Medical Center, Beilinson Campus, Petah Tikva, IsraelAnnat Raiter, The Laboratory of Cellular and Vascular Immunology, Felsenstein Medical Research Center, Tel-Aviv University, School of Medicine, Rabin Medical Center, Beilinson Campus, Petah Tikva, IsraelVera Gaydar, Eye Research Laboratory, Felsenstein Medical Research Center, Tel-Aviv University, School of Medicine, Rabin Medical Center, Beilinson Campus, ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5454088 Fri, 25 Nov 2011 17:42:44 +0100 5454088 Cryptotanshinone induces ER stress-mediated apoptosis in HepG2 and MCF7 cells http://www.medworm.com/index.php?rid=5454089&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh36h93g5l26q8h5p%2F Abstract   The endoplasmic reticulum (ER) is a central organelle in eukaryotic cells that functions in protein synthesis and maturation, and also functions as a calcium storage organelle. Perturbation of ER functions leads to ER stress, which has been previously associated with a broad variety of diseases. ER stress is generally regarded as compensatory, but prolonged ER stress can activate apoptotic pathways in damaged cells. For this reason, pharmacological interventions that effectively enhance tumor death through ER stress have been the subject of a great deal of attention for anti-cancer therapy. Cryptotanshinone, the major active constituent isolated from the root of Salvia miltiorrhiza Bunge, has been recently evaluated for its anti-cancer activity, but the molecular... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5454089 Wed, 23 Nov 2011 17:43:08 +0100 5454089 The immunomodulatory drug lenalidomide restores a vitamin D sensitive phenotype to the vitamin D resistant breast cancer cell line MDA-MB-231 through inhibition of BCL-2: potential for breast cancer therapeutics http://www.medworm.com/index.php?rid=5454090&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc4w8635p35353666%2F Abstract  1α,25-Dihydroxyvitamin D3, (1,25-D3) the biologically active form of vitamin-D, is well established as a cancer cell growth inhibitor in addition to maintaining bone mineralization. In breast cancer cells, inhibitory effects on angiogenesis, and metastasis have been observed together with enhancement of apoptosis and induction of cell cycle arrest. There is a correlation between vitamin-D receptor expression on breast cancer cells and patient survival. However vitamin-D resistance and hypercalcaemia are key limiting factors in clinical use. The IMiD® immunomodulatory drug lenalidomide, (Revlimid®, CC-5013) used in myeloma, can also modulate apoptotic and growth signalling. We studied whether lenalidomide treated breast cancer cells would acquire sensitivity to 1... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5454090 Tue, 22 Nov 2011 17:56:58 +0100 5454090 Hepatocellular apoptosis in mice is associated with early upregulation of mitochondrial glucose metabolism http://www.medworm.com/index.php?rid=5454091&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fuh704m5738433333%2F Abstract  Hepatocyte death due to apoptosis is a hallmark of almost every liver disease. Manipulation of cell death regulatory steps during the apoptotic process is therefore an obvious goal of biomedical research. To clarify whether metabolic changes occur prior to the characteristic apoptotic events, we used ex vivo multinuclear NMR-spectroscopy to study metabolic pathways of [U-13C]glucose in mouse liver during Fas-induced apoptosis. We addressed whether these changes could be associated with protection against apoptosis afforded by Epidermal Growth Factor (EGF). Our results show that serum alanine and aspartate aminotransferase levels, caspase-3 activity, BID cleavage and changes in cellular energy stores were not observed before 3 h following anti-Fas injection. H... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5454091 Tue, 22 Nov 2011 17:56:56 +0100 5454091 Inhibition of caspase mediated apoptosis restores muscle function after crush injury in rat skeletal muscle http://www.medworm.com/index.php?rid=5428089&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff74mtp8833736531%2F Abstract  Although muscle regeneration after injury is accompanied by apoptotic cell death, prolonged apoptosis inhibits muscle restoration. The goal of our study was to provide evidence that inhibition of apoptosis improves muscle function following blunt skeletal muscle injury. Therefore, 24 rats were used for induction of injury to the left soleus muscle using an instrumented clamp. All animals received either 3.3 mg/kg i.p. of the pan-caspase inhibitor Z-valinyl-alanyl-dl-aspartyl-fluoromethylketone (z-VAD.fmk) (n = 12 animals) or equivalent volumes of the vehicle solution DMSO (n = 12 animals) at 0 and 48 h after trauma. After assessment of the fast twitch and tetanic contraction capacity of the muscle at days 4 and 14 post injury, sampling ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5428089 Wed, 16 Nov 2011 17:59:47 +0100 5428089 Inhibition of checkpoint kinase 1 abrogates G2/M checkpoint activation and promotes apoptosis under heat stress http://www.medworm.com/index.php?rid=5404770&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5332806212437575%2F In conclusion, these findings indicate a novel molecular basis of G2/M checkpoint activation and apoptosis in cells exposed to HS. Content Type Journal ArticleCategory Original PaperPages 1-11DOI 10.1007/s10495-011-0660-7Authors Yukihiro Furusawa, Department of Radiological Sciences, Life Science Research Center, Graduate School of Medicine Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194 JapanTakashi Iizumi, Department of Radiological Sciences, Life Science Research Center, Graduate School of Medicine Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194 JapanYoshisada Fujiwara, Department of Radiological Sciences, Life Science Research Center, Graduate School of Medicine Pharmaceutical Sciences, University of Toyama, Sugitani... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5404770 Fri, 11 Nov 2011 12:49:23 +0100 5404770 Pleomorphic adenoma gene-like 2 regulates expression of the p53 family member, p73, and induces cell cycle block and apoptosis in human promonocytic U937 cells http://www.medworm.com/index.php?rid=5404771&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy62058q377912032%2F Abstract  The proto-oncogene, pleomorphic adenoma gene-like 2 (PLAGL2), is implicated in a variety of cancers including acute myeloid leukemia (AML), malignant glioma, colon cancer, and lung adenocarcinoma. There is additional evidence that PLAGL2 can function as a tumor suppressor by initiating cell cycle arrest and apoptosis. Interestingly, PLAGL2 has also been implicated in human myelodysplastic syndrome, a disease that is characterized by ineffective hematopoiesis and can lead to fatal cytopenias (low blood counts) as a result of increased apoptosis in the marrow, or, in about one-third of cases, can progress to AML. To gain a better understanding of the actions of PLAGL2 in human myeloid cells, we generated a stable PLAGL2-inducible cell line, using human promonocytic ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5404771 Thu, 10 Nov 2011 16:50:50 +0100 5404771 Ginsenoside-Rd potentiates apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells through the mitochondrial pathway http://www.medworm.com/index.php?rid=5404772&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff8525607j154602x%2F Abstract  Our previous studies showed that ginsenoside-Rd, a purified component from Panax notoginseng, inhibited cell proliferation and reversed basilar artery remodeling. The aim of this study was to investigate whether ginsenoside- Rd influences H2O2-induced apoptosis in basilar artery smooth muscle cells (BASMCs). The results showed that ginsenoside-Rd significantly potentiated H2O2-induced cell death and cell apoptosis. This resulted in a concentration-dependent reduction of the cell viability. Ginsenoside-Rd further increased cytochrome C release and caspase-9/caspase-3 activations, and reduced the stability of mitochondrial membrane potential (MMP) and the ratio of Bcl-2/Bax. Cyclosporine A, an inhibitor of mitochondrial-permeability transition, inhibited alteration o... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5404772 Thu, 10 Nov 2011 16:50:49 +0100 5404772 ER stress sensitizes cells to TRAIL through down-regulation of FLIP and Mcl-1 and PERK-dependent up-regulation of TRAIL-R2 http://www.medworm.com/index.php?rid=5404773&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F30776359025287v2%2F In this study we report that ER stress-inducing agents sensitizes both transformed and nontransformed cells to TRAIL-induced apoptosis. In addition, glucose-regulated protein of 78 kDa (GRP78) knockdown by RNA interference induces ER stress and facilitates apoptosis by TRAIL. We demonstrate that TRAIL death-inducing signaling complex (DISC) formation and early signaling are enhanced in ER stressed cells. ER stress alters the cellular levels of different apoptosis-related proteins including a decline in the levels of FLIP and Mcl-1 and the up-regulation of TRAIL-R2. Up-regulation of TRAIL-R2 following ER stress is dependent on the expression of PKR-like ER kinase (PERK) and independent of CAAT/enhancer binding protein homologous protein (CHOP) and Ire1α. Silencing of TRAIL-R2 ex... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5404773 Wed, 09 Nov 2011 17:56:35 +0100 5404773 HepG2 cells infected with Klebsiella pneumoniae show DNA laddering at apoptotic and necrotic stages http://www.medworm.com/index.php?rid=5375467&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgu535g21642160h1%2F This study investigated how the bacterial infection affected cell survival at the molecular level, in a cultured cell model. A strain of KP highly virulent in mice was isolated from a patient with liver abscess, and was used to infect HepG2 cells. The infected cells were examined for their viability, DNA fragmentation, and proteins involved in apoptosis or necrosis. We found that the infection decreased the viability of HepG2 cells at 4 hours (h) to 12 h post infection (pi). DNA ladders appeared 6–16 h pi and flow cytometry analysis showed apoptosis at 3–5 h pi, secondary necrosis at 6–9 h pi and primary necrosis at 8–9 h pi. Cleavages of Caspase 7, Caspase 9, α-Fodrin, and PARP were evident at 2–4 h pi. At 7 h pi, we observed the fo... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5375467 Fri, 28 Oct 2011 17:13:19 +0100 5375467 Evidence supporting a role for dihydroorotate dehydrogenase, bioenergetics, and p53 in selective teriflunomide-induced apoptosis in transformed versus normal human keratinocytes http://www.medworm.com/index.php?rid=5343532&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb04667q630741280%2F Abstract  We have demonstrated previously that the dihydroorotate dehydrogenase (DHODH) inhibitor teriflunomide (TFN) encourages apoptosis in transformed human keratinocytes. Here we sought to determine if this cytotoxic effect could be restricted to transformed keratinocytes relative to their normal human epidermal keratinocyte (NHEK) counterparts, and ascertain a potential mechanistic basis for the selectivity. The NHEK cells proliferated much slower than the premalignant HaCaT and malignant COLO 16 keratinocytes, and exogenous uridine added to the culture medium did not affect this growth. Similarly, DHODH expression and the bioenergetic characteristics of the normal cells were markedly dissimilar from those observed in the transformed cells indicating that de novo pyrim... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5343532 Wed, 19 Oct 2011 15:44:50 +0100 5343532 Activation of apoptotic signalling events in human embryonic stem cells upon Coxsackievirus B3 infection http://www.medworm.com/index.php?rid=5343533&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F30330v65170u0383%2F In this study we found that the hESCs are highly susceptible to CVB3 infection and display elevated apoptosis rates, thus emerging as suitable human non-transformed in vitro models to study CVB3-induced apoptosis and resulting relevant to understand CVBs pathogenesis. Content Type Journal ArticleCategory Original PaperPages 1-11DOI 10.1007/s10495-011-0668-zAuthors Leonardo Romorini, Laboratorio de Biología del Desarrollo Celular, LIAN, FLENI, Ruta 9, Km 52,5, Escobar, B1625XAF Buenos Aires, ArgentinaMaría E. Scassa, Laboratorio de Biología del Desarrollo Celular, LIAN, FLENI, Ruta 9, Km 52,5, Escobar, B1625XAF Buenos Aires, ArgentinaGuillermo Videla Richardson, Laboratorio de Biología del Desarrollo Celular, LIAN, FLENI, Ruta 9, Km 52,5, Escobar, B1625XAF Buenos Aires, Argenti... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5343533 Wed, 19 Oct 2011 15:44:49 +0100 5343533 The MCP-1/CCR2 axis in podocytes is involved in apoptosis induced by diabetic conditions http://www.medworm.com/index.php?rid=5343534&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4864235815342622%2F Abstract  Previous studies have demonstrated the importance of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of diabetic nephropathy in terms of inflammation, but the direct role of the MCP-1/CCR2 system on podocyte apoptosis under diabetic conditions has never been explored. In vitro, mouse podocytes were exposed to a medium containing 30 mM glucose (HG) with or without CCR2 siRNA or CCR2 inhibitor (RS102895). Podocytes were also treated with MCP-1 or TGF-β1 with or without anti-TGF-β1 antibody, CCR2 siRNA, or CCR2 inhibitor. In vivo, 20 db/m and 20 db/db mice were divided into two groups, and ten mice from each group were treated with RS102895. Western blot and Hoechst 33342 or TUNEL staining were performed to identify apoptosis. HG-induce... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5343534 Tue, 18 Oct 2011 05:45:14 +0100 5343534 p53-dependent regulation of Mcl-1 contributes to synergistic cell death by ionizing radiation and the Bcl-2/Bcl-XL inhibitor ABT-737 http://www.medworm.com/index.php?rid=5330687&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqn356g8556k1666n%2F Abstract  Treatment with the Bcl-2/Bcl-XL inhibitor ABT-737 is a promising novel strategy to therapeutically induce apoptotic cell death in malignant tumors such as glioblastomas. Although many studies have demonstrated that ABT-737 acts synergistically with chemotherapeutic drugs, the possibility of a combined treatment with ionizing radiation (IR) and ABT-737 has not yet been thoroughly investigated. Similarly, the relationship between p53 function and the pro-apoptotic effects of ABT-737 are still obscure. Here, we demonstrate that IR and ABT-737 synergistically induce apoptosis in glioblastoma cells. The sensitivity to ABT-737-mediated cell death is significantly increased by the IR-dependent accumulation of cells in the G2/M cell cycle phase. Wild type p53 function inh... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5330687 Fri, 14 Oct 2011 15:44:41 +0100 5330687 5-Phenylselenyl- and 5-methylselenyl-methyl-2′-deoxyuridine induce oxidative stress, DNA damage, and caspase-2-dependent apoptosis in cancer cells http://www.medworm.com/index.php?rid=5330688&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw2lg702k64157315%2F Abstract  In the present study, we investigated the signaling pathways implicated in the induction of apoptosis by two modified nucleosides, 5-phenylselenyl-methyl-2′-deoxyuridine (PhSe-T) and 5-methylselenyl-methyl-2′-deoxyuridine (MeSe-T), using human cancer cell lines. The induction of apoptosis was associated with proteolytic activation of caspase-3 and -9, PARP cleavage, and decreased levels of IAP family members, including c-IAP-1 and c-IAP-2, but had no effect on XIAP and survivin. PhSe-T and MeSe-T also enhanced the activities of caspase-2 and -8, Bid cleavage, and the conformational activation of Bax. Additionally, nucleoside derivative-induced apoptosis was inhibited by the selective inhibitors of caspase-2, -3, -8, and -9 and also by si-RNAs against caspase-2... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5330688 Fri, 14 Oct 2011 10:39:56 +0100 5330688 p66Shc-dependent apoptosis requires Lck and CamKII activity http://www.medworm.com/index.php?rid=5310787&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3nx3471k17u68rm5%2F Abstract  p66Shc, an adaptor molecule which enhances reactive oxygen species (ROS) production by mitochondria, promotes T-cell apoptosis by inducing mitochondrial dysfunction and impairing Ca2+ homeostasis. We have addressed the potential role of Lck, a kinase which has been implicated in T-cell apoptosis induced by a number of stimuli, in the proapoptotic activity of p66Shc. Lck deficiency in Jurkat T cells overexpressing p66Shc leads to impaired apoptotic responses to supraphysiological increases in [Ca2+]c. This defect could be rescued by reconstitution of Lck expression, indicating that Lck is required for p66Shc-dependent apoptosis. Furthermore, p66Shc phosphorylation on serine 36 (S36), an event on which the proapoptotic function of p66Shc depends, requires Lck. p66Shc... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5310787 Sat, 08 Oct 2011 15:44:05 +0100 5310787 Modulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model in vitro http://www.medworm.com/index.php?rid=5301844&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb823679613053685%2F Abstract  TRAIL (TNF-related apoptosis-inducing ligand) has been shown to induce apoptosis by binding to TRAIL-R1 and -R2 death receptors, but not to TRAIL-R3 or -R4, its decoy receptors that lack the internal death domain. Osteoclasts (Ocs) are sensitive to TRAIL-induced apoptosis, and modulation of these receptors may change Oc sensitivity to TRAIL. Using human Oc cultures, we first investigated the gene expression profile of these receptors (TNFRSF10 -A, -B, -C, -D encoding TRAIL-Rs 1–4) by real time PCR after adding osteotropic factors during the last week of Oc cultures. We observed a significant decrease in the expression of TNFRSF10-A after the addition of TGFβ, and an increase in that of TNFRSF10-A and -B post-PTH stimulation. Protein expression of TRAIL-R1 and -R3... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5301844 Wed, 05 Oct 2011 05:46:35 +0100 5301844 Mammalian target of rapamycin regulates isoliquiritigenin-induced autophagic and apoptotic cell death in adenoid cystic carcinoma cells http://www.medworm.com/index.php?rid=5281494&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp5047277383p3110%2F Abstract  Previous studies, including those from our laboratory, have demonstrated that isoliquiritigenin (ISL), a flavonoid isolated from licorice, is a promising cancer chemotherapeutic agent. However the mechanisms underlying its anticancer effects are still far from clear. We now show, for the first time, that ISL triggers the mammalian target of rapamycin (mTOR)-dependent autophagic and apoptotic cell death in adenoid cystic carcinoma (ACC). Exposure of both ACC-2 and ACC-M cells to ISL resulted in several specific features for autophagy, including the appearance of membranous vacuoles, formation of acidic vesicular organelles, punctate pattern of LC3 immunostaining, and an increase in autophagic flux. Moreover, ISL treatment also resulted in significantly increased ap... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5281494 Thu, 29 Sep 2011 06:07:06 +0100 5281494 Elevated skeletal muscle apoptotic signaling following glutathione depletion http://www.medworm.com/index.php?rid=5257302&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe234154255523kh4%2F Abstract  Oxidative stress has a well-established role in numerous intracellular signaling pathways, including apoptosis. Glutathione is an important cellular antioxidant and is the most abundant low molecular weight thiol in the cell. Although previous work has shown a link between glutathione and apoptosis, this relationship has not been defined in skeletal muscle. The present investigation examined the effect of glutathione depletion on skeletal muscle apoptotic signaling, and mitochondrial apoptotic-susceptibility. Administration of l-buthionine-[S,R]-sulfoximine (BSO; 30 mM in drinking water for 10 days) caused glutathione depletion in whole muscle and isolated mitochondria, as well as elevated muscle catalase protein content and reactive oxygen species (ROS) ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5257302 Sat, 24 Sep 2011 15:47:04 +0100 5257302 β-Amyloid protein (Aβ) and human amylin regulation of apoptotic genes occurs through the amylin receptor http://www.medworm.com/index.php?rid=5257303&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx734474g70r21081%2F In this study, we utilized RT-PCR arrays to compare RNA expression levels of 84 markers for pro and anti- apoptotic signalling pathways following exposure of HFNs to either Aβ1-42 (20 μM) or human amylin (2 μM). Oligomeric Aβ1-42 or human amylin was applied to HFNs alone or after pre-treatment of cultures with the amylin receptor antagonist, AC253. Changes in RNA levels were then quantified and compared to each other in order to identify increases or decreases in gene expression of apoptotic markers. Applications of Aβ1-42 or human amylin, but not the inactive inverse sequence Aβ42-1 or rat amylin, resulted in a time-dependent marked increase in mediators of apoptosis including a 10- to 30-fold elevations in caspases 3, 6, 9, BID and XIAP levels. Amylin receptor antago... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5257303 Fri, 23 Sep 2011 16:19:04 +0100 5257303 Ras signaling in NGF reduction and TNF-α-related pancreatic β cell apoptosis in hyperglycemic rats http://www.medworm.com/index.php?rid=5257305&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff2q172770157u841%2F Abstract  Recent evidence suggested that tumor necrosis factor-alpha (TNF-α) and nerve growth factor (NGF) withdrawal activated a common apoptotic pathway. Here, we aimed to investigate the possible role of apoptotic Ras effectors RASSF1 and NORE1 in NGF reduction and TNF-α-related β cell apoptosis in streptozotocin (STZ)-induced hyperglycemic rats. Rats were divided into four groups: the first group was given saline and citrate buffer, the second group was injected 4-methylcatechol (4-MC), an inducer of NGF synthesis, the third group received STZ, and the fourth group was given both 4-MC and STZ. 4-MC (10 μg/kg) was administered by daily intraperitoneal injection for 10 days before the animals were rendered hyperglycemic by administration of single dose STZ (... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5257305 Thu, 22 Sep 2011 06:01:08 +0100 5257305 Inhibition of deoxycholate-induced apoptosis in iron-depleted HCT-116 cells http://www.medworm.com/index.php?rid=5257304&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp5h1wm6tn525364t%2F Abstract  The bile acid, deoxycholate (DOC), can induce apoptosis in cells containing adequate amounts of all key nutrients, but it is unknown whether DOC-induced apoptosis can occur in cells lacking a single key nutrient. The aim of this study was to determine if DOC is able to induce apoptosis in HCT-116 colon epithelial cells depleted of iron. The cells were made iron-deficient by pre-treating them with the iron chelator, deferoxamine (DFO), before subsequent exposure to DOC. Mitochondrial dysfunction was detected in control cells exposed to DOC, but not in iron-depleted cells exposed to DOC. Moreover, characteristic features of apoptosis, namely, membrane blebbing, formation of apoptotic bodies, cytochrome c release into cytosol, generation of the activated form of caspa... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5257304 Thu, 22 Sep 2011 06:01:08 +0100 5257304 Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo http://www.medworm.com/index.php?rid=5233513&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk7v08q63rhn60w05%2F Abstract  Vascular endothelial cell (VEC) apoptosis is the main event occurring during the development of atherosclerosis. Pterostilbene (PT), a natural dimethylated analog of resveratrol, has been the subject of intense research in cancer and inflammation. However, the protective effects of PT against oxidized low-density lipoprotein (oxLDL)-induced apoptosis in VECs have not been clarified. We investigated the anti-apoptotic effects of PT in vitro and in vivo in mice. PT at 0.1–5 μM possessed antioxidant properties comparable to that of trolox in a cell-free system. Exposure of human umbilical vein VECs (HUVECs) to oxLDL (200 μg/ml) induced cell shrinkage, chromatin condensation, nuclear fragmentation, and cell apoptosis, but PT protected against such injurie... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5233513 Sat, 17 Sep 2011 17:06:32 +0100 5233513 Effects of cucurbitacins on cell morphology are associated with sensitization of renal carcinoma cells to TRAIL-induced apoptosis http://www.medworm.com/index.php?rid=5233515&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj08432011l234635%2F Abstract  Cucurbitacins B and D were among the compounds identified as sensitizers of cancer cells to TRAIL-mediated apoptosis in a high-throughput screen. Therefore a series of cucurbitacins was further investigated for TRAIL sensitization and possible mechanisms of action. A total of six cucurbitacins promoted TRAIL-induced apoptosis (B, I, E, C, D, and K) and one (P) was inactive. Sensitization of renal adenocarcinoma cells to TRAIL was apparent after as little as 1–4 h pretreatment and did not require continued presence of cucurbitacin. Active cucurbitacins induced caspase-8 activation only after subsequent TRAIL addition and caspase activation was required for apoptosis suggesting amplified proximal signaling from TRAIL death receptors. Cucurbitacin-sensitized T... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5233515 Sat, 17 Sep 2011 17:06:31 +0100 5233515 Protective effect of melittin on inflammation and apoptosis in acute liver failure http://www.medworm.com/index.php?rid=5233514&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3u25324m78tv4635%2F Abstract  Acute hepatic failure remains an extremely poor prognosis and still results in high mortality. Therefore, better treatment is urgently needed. Melittin, a major component of bee venom, is known to inhibit inflammatory reactions induced by lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α in various cell types. However, there is no evidence of the anti-inflammatory and anti-apoptotic effect of melittin on liver cells. In the present study, we investigated the effects of melittin on d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced acute hepatic failure. Acute liver injury was induced with GalN/LPS to determine in vivo efficacy of melittin. Mice were randomly divided into four groups: sterile saline treated group (NC), melittin only treated group (NM),... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5233514 Sat, 17 Sep 2011 17:06:31 +0100 5233514 Suppression of matrix metalloproteinase-9 expression in undifferentiated, non-apoptotic keratinocytes is abrogated by the cleavage of poly(ADP-ribose) polymerase-1 http://www.medworm.com/index.php?rid=5233516&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw1288780875646j0%2F This study demonstrates the regulation of MMP-9 transcription through a gene regulatory element in its promoter (the KRE-M9 element). The KRE-M9-binding protein was purified and identified as poly(ADP-ribose) polymerase-1 (PARP-1), which inhibits the transcription of MMP-9 similar to involucrin. This regulation occurs in non-apoptotic keratinocytes using the distinctive culture conditions of high and low Ca2+ levels. PARP cleavage, which occurs during apoptosis, results in de-repression of MMP-9 promoter activity. These data clarify a new role of PARP-1 and suggest a physiologically relevant connection between caspase activation and MMP-9 expression. Content Type Journal ArticleCategory Original PaperPages 1-12DOI 10.1007/s10495-011-0650-9Authors Takashi Kobayashi, Department of... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5233516 Wed, 14 Sep 2011 05:52:39 +0100 5233516 Fas/FasL pathway-mediated alveolar macrophage apoptosis involved in human silicosis http://www.medworm.com/index.php?rid=5217701&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn527320314576j84%2F Abstract  In vitro and in vivo studies have demonstrated that lung cell apoptosis is associated with lung fibrosis; however the relationship between apoptosis of alveolar macrophages (AMs) and human silicosis has not been addressed. In the present study, AM apoptosis was determined in whole-lung lavage fluid from 48 male silicosis patients, 13 male observers, and 13 male healthy volunteers. The relationships between apoptosis index (AI) and silica exposure history, soluble Fas (sFas)/membrane-bound Fas (mFas), and caspase-3/caspase-8 were analyzed. AI, mFas, and caspase-3 were significantly higher in lung lavage fluids from silicosis patients than those of observers or healthy volunteers, but the level of sFas demonstrated a decreasing trend. AI was related to silica exposu... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5217701 Sat, 10 Sep 2011 15:47:06 +0100 5217701 Regulation of apoptosis in human melanoma and neuroblastoma cells by statins, sodium arsenite and TRAIL: a role of combined treatment versus monotherapy http://www.medworm.com/index.php?rid=5217702&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd401m84w77129v46%2F Abstract  Treatment of melanoma cells by sodium arsenite or statins (simvastatin and lovastatin) dramatically modified activities of the main cell signaling pathways resulting in the induction of heme oxygenase-1 (HO-1) and in a downregulation of cyclooxygenase-2 (COX-2) protein levels. Through heme degradation and the production of carbon monoxide and biliverdin, HO-1 plays a protective role in different scenario of oxidative stress followed by mitochondrial apoptosis. Both sodium arsenite and statins could be efficient inducers of apoptosis in some melanoma cell lines, but often exhibited only modest proapoptotic activity in others, due to numerous protective mechanisms. We demonstrated in the present study that treatment by sodium arsenite or statins with an additional i... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5217702 Sat, 10 Sep 2011 15:47:04 +0100 5217702 A rapid detection method for apoptosis and necrosis measurement using the Cellometer imaging cytometry http://www.medworm.com/index.php?rid=5217703&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5173732u8gw583x3%2F In this study, we demonstrate for the first time the use of Cellometer imaging cytometry for necrosis/apoptosis detection by studying the dose–response effect of heat and drug-induced cell death in Jurkat cells labeled with annexin V-FITC (apoptotic) and propidium iodide (necrotic). The experimental results were evaluated to validate the imaging cytometric capabilities of the Cellometer system as compared to the conventional flow cytometry. Similar cell population results were obtained from the two methods. The ability of Cellometer to rapidly and cost-effectively perform fluorescent cell-based assays has the potential of improving research efficiency, especially where a flow or laser scanning cytometer is not available or in situations where a rapid analysis of data is desired. ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5217703 Sat, 10 Sep 2011 15:47:03 +0100 5217703 The pro-apoptotic protein Prostate Apoptosis Response Protein-4 (Par-4) can be activated in colon cancer cells by treatment with Src inhibitor and 5-FU http://www.medworm.com/index.php?rid=5217704&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk44m234g06673812%2F Abstract  The overexpression of the pro-apoptotic protein Prostate Apoptosis Response Protein-4 in colon cancer has been shown to increase response to the chemotherapeutic agent 5-fluorouracil (5-FU). Although colon cancer cells endogenously express Par-4, the presence or overexpression of Par-4 alone does not cause apoptosis. We hypothesize that Par-4 is inactivated in colon cancer. In colon cancer, the levels and the kinase activity of the nonreceptor tyrosine kinase c-Src increase with tumor progression. One of the downstream effectors of c-Src is Akt1. Akt1 has been shown to inhibit the pro-apoptotic activity of Par-4 in prostate cancer cells. We therefore investigated the potential of activating Par-4 by inhibiting c-Src. Colon carcinoma cell lines were treated with th... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5217704 Sat, 10 Sep 2011 15:47:02 +0100 5217704 Review: milk fat globule-EGF factor 8 expression, function and plausible signal transduction in resolving inflammation http://www.medworm.com/index.php?rid=5217705&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F280w63267504h011%2F Abstract  Although the cloning and molecular characterization of MFG-E8 was first reported in the early 90s, breakthrough on MFG-E8 research came into light when it was explored as an outstanding factor for phagocytosis of apoptotic cells by professional macrophages in 2002. Since then numerous studies have been performed on MFG-E8 not only to demonstrate the role of phagocytic clearance of apoptotic cells, but also to focus on a wide range of aspects, even emphasizing on a direct link to innate-immune systems. In terms of its role as therapeutic potentials, our group, as well as others, has shown MFG-E8 to be an essential factor in attenuating inflammation and improving prognosis in several animal models of life threatening diseases. Considering these versatile functions o... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5217705 Thu, 08 Sep 2011 06:05:41 +0100 5217705 Glutamate dehydrogenase requirement for apoptosis induced by aristolochic acid in renal tubular epithelial cells http://www.medworm.com/index.php?rid=5217706&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg17323t3n5253355%2F We report that AA induces cell death in GDH-knockdown TEC preferentially via non-apoptotic means, whereas in GDH-positive cells, death was executed by both the non-apoptotic and apoptotic mechanisms. Apoptosis is an energy-reliant process and demands higher adenosine 5′-triphosphate (ATP) consumption than does the non-apoptotic cell death. We found that, after AAI treatment, the ATP depletion is more pronounced in GDH-knockdown cells. When we reduced ATP in TEC cells by inhibition of glycolysis and mitochondrial respiration, cell death mode switched from apoptosis and necrosis to necrosis only. In addition, in cells incubated at low glucose and no glutamine conditions, oxaloacetate and pyruvate reduced AAI-induced apoptosis our data suggest that AAI-GDH interactions in TEC are crit... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5217706 Thu, 08 Sep 2011 06:05:40 +0100 5217706 Role of death receptor, mitochondrial and endoplasmic reticulum pathways in different stages of degenerative human lumbar disc http://www.medworm.com/index.php?rid=5191225&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm1v6476g13366780%2F In conclusion, apoptosis occurs via these three apoptosis pathways together in IVDD. ER pathway plays a more critical role in the mild compared to moderate and severe stages, death receptor pathway in mild and moderate, and mitochondrial pathway in moderate and severe stages of IVDD. Disc cells apoptosis may progress rapidly after herniation, and may depend on the type of herniation. Content Type Journal ArticleCategory Original PaperPages 1-14DOI 10.1007/s10495-011-0644-7Authors Hua Wang, Department of Orthopaedics, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, 510080 ChinaHui Liu, Department of Orthopaedics, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, 510080 ChinaZhao-Min Zheng, Department... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5191225 Tue, 30 Aug 2011 15:59:10 +0100 5191225 Perturbation of intracellular K+ homeostasis with valinomycin promotes cell death by mitochondrial swelling and autophagic processes http://www.medworm.com/index.php?rid=5191226&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr20p274n43977x84%2F Abstract  Perturbation of cellular K+ homeostasis is a common motif in apoptosis but it is unknown whether a decrease in intracellular K+ alone is sufficient to replicate apoptotic hallmarks. We investigated, which mode of cell death is induced by decreasing the intracellular K+ concentration using valinomycin, a highly K+-selective ionophore. Valinomycin treatment induced mitochondrial swelling and minor nuclear changes in cell lines (BV-2, C6, HEK 293), and in primary mouse microglia and astrocytes. In the microglial cell line BV-2, we identified and quantified three phenotypes in valinomycin-exposed cells. The first and most prevalent phenotype (62 ± 2%) was characterized by swollen mitochondria and no chromatin condensation, and the second (25 ± 3%) ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5191226 Mon, 29 Aug 2011 16:00:31 +0100 5191226 Heterogeneity of primary glioblastoma cells in the expression of caspase-8 and the response to TRAIL-induced apoptosis http://www.medworm.com/index.php?rid=5191227&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg022l1nm86246113%2F This study shows heterogeneity of glioblastomas and derived CSCs in the genomic status of CASP8, expression of caspase-8, and thus responsiveness to TRAIL-induced apoptosis. Clinic trials may consider genomic analysis of the cancer tissue to identify the genomic loss of CASP8 and use it as a genomic marker to predict the resistance of glioblastomas to TRAIL apoptosis pathway-targeted therapies. Content Type Journal ArticleCategory Original PaperPages 1-15DOI 10.1007/s10495-011-0645-6Authors Ling Qi, Department of Pathology & Laboratory Medicine, Radiation Oncology, and Neurosurgery, Winship Cancer Institute, Emory University School Medicine, 1365-C Clifton Road, Atlanta, GA 30322, USAAnita C. Bellail, Department of Pathology & Laboratory Medicine, Radiation Oncology, and Neurosurg... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5191227 Mon, 29 Aug 2011 16:00:29 +0100 5191227 Rapamycin protects against dominant negative-HNF1A-induced apoptosis in INS-1 cells http://www.medworm.com/index.php?rid=5173937&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj72214451056k31p%2F Abstract  HNF1A-maturity onset diabetes of the young (HNF1A-MODY) is caused by mutations in Hnf1a gene encoding the transcription factor hepatocyte nuclear factor 1alpha (HNF1A). An increased rate of apoptosis has been associated with the decrease in beta-cell mass that is a hallmark of HNF1A-MODY and other forms of diabetes. In a cellular model of HNF1A-MODY, we have recently shown that signalling through mammalian target of rapamycin (mTOR) is decreased by the overexpression of a dominant-negative mutant of HNF1A (DN-HNF1A). mTOR is a protein kinase which has important roles in cell metabolism and growth, but also in cell survival, where it has been shown to be both protective and detrimental. Here, we show that pharmacological inhibition of mTOR activity with rapamycin pr... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5173937 Sat, 27 Aug 2011 05:55:46 +0100 5173937 Alteration in inflammatory/apoptotic pathway and histone modifications by nordihydroguaiaretic acid prevents acute pancreatitis in swiss albino mice http://www.medworm.com/index.php?rid=5173936&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftp18x42x16210052%2F Abstract  Reactive oxygen radicals, pro-inflammatory mediators and cytokines have been implicated in caerulein induced acute pancreatitis. Nordihydroguaiaretic acid (NDGA), a plant lignin, has marked anti-inflammatory properties. The present study aimed to investigate the possible protective effect of NDGA against caerulein induced pancreatitis. Acute pancreatitis was induced by intraperitoneal administration of eight doses of caerulein in male swiss albino mice. NDGA was administered after 9 h of acute pancreatitis induction. Pancreatic damage and the protective effect of NDGA were assessed by oxidative stress parameters and histopathology of pancreas. The mRNA expression of heat shock proteins (DNAJ C15 and HSPD1) was examined by real-time RT-PCR analysis. Expression ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5173936 Sat, 27 Aug 2011 05:55:46 +0100 5173936 Terfenadine induces apoptosis and autophagy in melanoma cells through ROS-dependent and -independent mechanisms http://www.medworm.com/index.php?rid=5168899&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu2v287l784311151%2F In this report, focusing our attention on the apoptotic mechanisms activated by terfenadine, we show that this drug can potentially activate distinct intrinsic signaling pathways depending on culture conditions. Serum-deprived conditions enhance the cytotoxic effect of terfenadine and caspase-4 and -2 are activated upstream of caspase-9. Moreover, although we found an increase in ROS levels, the apoptosis was ROS independent. Conversely, terfenadine treatment in complete medium induced ROS-dependent apoptosis. Caspase-4, -2, and -9 were simultaneously activated and p73 and Noxa induction were involved. ROS inhibition prevented p73 and Noxa expression but not p53 and p21 expression, suggesting a role for Noxa in p53-independent apoptosis in melanoma cells. Finally, we found that terfe... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5168899 Tue, 23 Aug 2011 05:56:41 +0100 5168899 Type I IFNs signaling and apoptosis resistance in glioblastoma cells http://www.medworm.com/index.php?rid=5155694&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5366394734788221%2F Abstract  Deletion of type I IFN genes and resistance to apoptosis induced by type I IFNs are common in glioblastoma. Here we have investigated the importance of the constitutive weak IFN-signaling in the apoptotic response to IFN-α in glioblastoma cells. U87MG cells hold a deletion of type I IFN genes, whereas in T98G cells the spontaneous IFN signaling is intact. In response to IFN-α U87MG cells produce much less TRAIL, while other IFN-inducible genes were efficiently up-regulated. Alterations in TRAIL promoter sequence and activity were not observed. DNA methylation can influence TRAIL transcription but without overt differences between the two cell lines. We also discovered that TRAIL mRNA stability is influenced by IFN-α, but again no differences can be appreciated ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5155694 Sat, 20 Aug 2011 15:51:27 +0100 5155694 The natural diterpene ent-16β-17α-dihydroxykaurane down-regulates Bcl-2 by disruption of the Ap-2α/Rb transcription activating complex and induces E2F1 up-regulation in MCF-7 cells http://www.medworm.com/index.php?rid=5155695&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq2m938843n57601l%2F Abstract  ent-Kauranes are diterpene-type compounds commonly found in most plant species, especially from the Euphorbiaceae family. These compounds have been studied due to their anti-inflammatory and anti-tumor properties. Regulation of apoptosis, or programmed cell death, is commonly bypassed by tumoral cells, giving rise to uncontrolled proliferating cells, which eventually become carcinogenic. In a previous work, we showed that both mRNA and protein expression levels of the antiapoptotic gene Bcl-2 are reduced in MCF-7 cancer cells by the effect of the natural diterpene ent-16β-17α-dihydroxykaurane (DHK). This effect was not directly associated with the inactivation of NF-κB, as has been shown with other diterpenes compounds. Herein, we report that DHK is dissociatin... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5155695 Thu, 18 Aug 2011 05:48:25 +0100 5155695 JWA enhances As2O3-induced tubulin polymerization and apoptosis via p38 in HeLa and MCF-7 cells http://www.medworm.com/index.php?rid=5155696&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk5466w7523l38120%2F Abstract  Arsenic trioxide (As2O3) has potential anti-cancer activity against a wide range of carcinomas via apoptosis induction or oncoprotein degradation. The mechanisms involved are not fully elucidated. Here, we demonstrated that As2O3 induced-apoptosis in HeLa and MCF-7 cancer cells was in part triggered by tubulin polymerization. High expression of JWA promoted tubulin polymerization and increased the sensitivity of the cancer cells to As2O3. The activation of the p38 MAPK (mitogen-activated protein kinases) signaling pathway was found to contribute to JWA-promoted tubulin polymerization. Our results suggest that JWA may serve as an effective enhancer of microtubule-targeted As2O3 anti-cancer therapy. Content Type Journal ArticleCategory Original PaperPages 1-17DOI ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5155696 Wed, 17 Aug 2011 06:02:39 +0100 5155696 Cellular imaging assay for early evaluation of an apoptosis inducer http://www.medworm.com/index.php?rid=5124422&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fepw11h552u78g552%2F The objective of this study was to propose a feasibility of a cellular imaging assay as an alternative to the conventional cytotoxicity assay, such as MTS assay, for apoptosis monitoring. As an apoptosis monitoring parameter, affinity interaction between phosphatidylserine (PS) and annexin V was chosen. First, the specific binding affinity between annexin V and PS in phospholipid bilayers consisting of various molar (0–15%) composition of PS was measured using a surface plasmon resonance biosensor. As PS composition increased, the binding level of annexin V increased proportionally. Second, various concentrations (0.1–10 μM) of staurosporine were used as to induce apoptosis and introduced to MCF-7 breast carcinoma cells. The cellular fluorescence images from annexin V-FITC ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5124422 Wed, 10 Aug 2011 15:45:29 +0100 5124422 Camptothecin induces p53-dependent and -independent apoptogenic signaling in melanoma cells http://www.medworm.com/index.php?rid=5102772&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj763775826255700%2F Abstract  Various DNA-targeting agents may initiate p53-dependent as well as p53-independent response and subsequent apoptosis via alternative cellular systems which include for instance p73, caspase-2 or Bcl-2 family proteins. The scope of involvement of individual molecules in this process and the mechanisms governing their potential interplay are still not entirely understood, in particular in highly aggressive cancers such as in malignant melanoma. In this work we investigated the role and involvement of both p53-dependent and -independent mechanisms in selected melanoma cell lines with differing status of p53 using a model DNA topoisomerase I inhibitor camptothecin (CPT). Here we report that CPT induced in Bowes melanoma cells apoptosis which is essentially p53 and mit... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5102772 Tue, 02 Aug 2011 06:16:11 +0100 5102772 Deoxycholic and chenodeoxycholic bile acids induce apoptosis via oxidative stress in human colon adenocarcinoma cells http://www.medworm.com/index.php?rid=5076406&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm3716n6580707g97%2F Abstract  The continuous exposure of the colonic epithelium to high concentrations of bile acids may exert cytotoxic effects and has been related to pathogenesis of colon cancer. A better knowledge of the mechanisms by which bile acids induce toxicity is still required and may be useful for the development of new therapeutic strategies. We have studied the effect of deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) treatments in BCS-TC2 human colon adenocarcinoma cells. Both bile acids promote cell death, being this effect higher for CDCA. Apoptosis is detected after 30 min–2 h of treatment, as observed by cell detachment, loss of membrane asymmetry, internucleosomal DNA degradation, appearance of mitochondrial transition permeability (MPT), and caspase an... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5076406 Tue, 26 Jul 2011 05:53:08 +0100 5076406 Celastrol inhibits tumor cell proliferation and promotes apoptosis through the activation of c-Jun N-terminal kinase and suppression of PI3 K/Akt signaling pathways http://www.medworm.com/index.php?rid=5061508&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fnk128748h051t784%2F Abstract  Celastrol, a plant triterpene has attracted great interest recently, especially for its potential anti-inflammatory and anti-cancer activities. In the present report, we investigated the effect of celastrol on proliferation of various cancer cell lines. The mechanism, by which this triterpene exerts its apoptotic effects, was also examined in detail. We found that celastrol inhibited the proliferation of wide variety of human tumor cell types including multiple myeloma, hepatocellular carcinoma, gastric cancer, prostate cancer, renal cell carcinoma, head and neck carcinoma, non-small cell lung carcinoma, melanoma, glioma, and breast cancer with concentrations as low as 1 μM. Growth inhibitory effects of celastrol correlated with a decrease in the levels of c... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5061508 Sat, 23 Jul 2011 15:48:58 +0100 5061508 Insulin-like growth factor-1 receptor activation prevents hydrogen peroxide-induced oxidative stress, mitochondrial dysfunction and apoptosis http://www.medworm.com/index.php?rid=5061509&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm83427827636jq14%2F Abstract  Vascular disease is the leading cause of morbidity and mortality. Oxidative stress can cause endothelial cell apoptosis. Low insulin like growth factor-1 (IGF-1) has been linked to adverse risk profile and increased vascular disease incidence. Since IGF-1 acts as an important survival factor for multiple cell types, we undertook this study to investigate whether IGF-1 favorably affects oxidative-stress mediated apoptosis of vascular endothelial cells. Exposure to hydrogen peroxide induced apoptotic changes (e.g. DNA fragmentation, altered mitochondrial membrane potential and caspase-3 activity) in human umbilical vein endothelial cells (HUVECs) in a time dependent manner. Addition of IGF-1 blocked the oxidative-stress effect parallel to IGF-1 receptor (IGF-1R) exp... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5061509 Fri, 22 Jul 2011 16:56:55 +0100 5061509 Dietary anthocyanins protect endothelial cells against peroxynitrite-induced mitochondrial apoptosis pathway and Bax nuclear translocation: an in vitro approach http://www.medworm.com/index.php?rid=5061510&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fll243026072827h7%2F Abstract  Anthocyanins have received increasing attention because of their relatively high intake in humans and wide range of potential health-promoting effects, including anti-atherogenic properties. Evidences support their vascular protective effects but the involved molecular mechanisms have not been well clarified. The endothelium seems to have a central role in atherogenesis and apoptosis is emerging as a crucial event in this disease progression. Following our previous work on the biochemical pathways underlying peroxynitrite-triggered apoptosis in endothelial cells, here we investigated potential mechanisms responsible for the cytoprotective actions of three common anthocyanins, namely cyanidin- delphinidin- and pelargonidin-3-glucoside, against this process. Beyond ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5061510 Fri, 22 Jul 2011 16:56:53 +0100 5061510 Silibinin triggers apoptotic signaling pathways and autophagic survival response in human colon adenocarcinoma cells and their derived metastatic cells http://www.medworm.com/index.php?rid=5061511&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcn6461q405110656%2F Abstract  Silibinin, a flavonolignan isolated from the milk thistle plant (Silybum marianum), possesses anti-neoplastic properties. In vitro and in vivo studies have recently shown that silibinin inhibits the growth of colorectal cancer (CRC). The present study investigates the mechanisms of silibinin-induced cell death using an in vitro model of human colon cancer progression, consisting of primary tumor cells (SW480) and their derived metastatic cells (SW620) isolated from a metastasis of the same patient. Silibinin induced apoptotic cell death evidenced by DNA fragmentation and activation of caspase-3 in both cell lines. Silibinin enhanced the expression (protein and mRNA) of TNF-related apoptosis-inducing ligand (TRAIL) death receptors (DR4/DR5) at the cell surface in SW... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5061511 Thu, 21 Jul 2011 18:02:05 +0100 5061511 Valinomycin induced energy-dependent mitochondrial swelling, cytochrome c release, cytosolic NADH/cytochrome c oxidation and apoptosis http://www.medworm.com/index.php?rid=5017854&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3tv6263150j70310%2F Abstract  In valinomycin induced stimulation of mitochondrial energy dependent reversible swelling, supported by succinate oxidation, cytochrome c (cyto-c) and sulfite oxidase (Sox) [both present in the mitochondrial intermembrane space (MIS)] are released outside. This effect can be observed at a valinomycin concentration as low as 1 nM. The rate of cytosolic NADH/cyto-c electron transport pathway is also greatly stimulated. The test on the permeability of mitochondrial outer membrane to exogenous cyto-c rules out the possibility that the increased rate of exogenous NADH oxidation could be ascribed either to extensively damaged or broken mitochondria. Accumulation of potassium inside the mitochondria, mediated by the highly specific ionophore valinomycin, promotes an i... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5017854 Fri, 08 Jul 2011 06:37:00 +0100 5017854 The non-steroidal anti-inflammatory drugs Sulindac sulfide and Diclofenac induce apoptosis and differentiation in human acute myeloid leukemia cells through an AP-1 dependent pathway http://www.medworm.com/index.php?rid=5017856&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fal2l378802254777%2F In this study, a total number of 42 bone marrow derived CD34+ selected de novo AML patient samples and the AML cell lines THP-1 and HL-60 were treated with the NSAIDs Sulindac sulfide and Diclofenac. We analyzed viability, apoptosis, differentiation and addressed the molecular mechanisms involved. We found a consistent induction of apoptosis and to some extent an increased myeloid differentiation capacity in NSAID treated AML cells. Comprehensive protein and gene expression profiling of Diclofenac treated AML cells revealed transcriptional activation of GADD45α and its downstream MAPK/JNK pathway as well as increased protein levels of the caspase-3 precursor. This pointed towards a role of the c-Jun NH2-terminal kinase (JNK) in NSAID mediated apoptosis that we found indeed to be dep... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5017856 Fri, 08 Jul 2011 06:36:59 +0100 5017856 Follicular atresia in the prepubertal spiny mouse (Acomys cahirinus) ovary http://www.medworm.com/index.php?rid=5017855&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj88410gh20448r17%2F This study was designed to determine follicular atresia in the newborn and the prepubertal spiny mouse. We analyzed the processes of follicle loss using classical markers of apoptosis (TUNEL reaction, active caspase-3) and autophagy (Lamp1). Numerous small clear vacuoles and autophagosomes as well as strong Lamp1 staining were observed in dying oocytes of all follicle types, especially of the primordial and primary ones. Active caspase 3 and the TUNEL reaction were detected only in the granulosa cells of large secondary and antral follicles. The expression of apoptosis and autophagy markers was also changing during the prepubertal period. Western blot analysis indicated that at the moment of birth, females undergo an increased rate of follicular atresia mediated by autophagy, while a... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5017855 Fri, 08 Jul 2011 06:36:59 +0100 5017855 Translocation and oligomerization of Bax is regulated independently by activation of p38 MAPK and caspase-2 during MN9D dopaminergic neurodegeneration http://www.medworm.com/index.php?rid=5017857&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr544g7553r7v7436%2F Abstract  Bax is translocated into the mitochondrial membrane and oligomerized therein to initiate mitochondrial apoptotic signaling. Our previous study indicated that reactive oxygen species (ROS)-mediated activation of mitogen-activated protein kinase (MAPK) and caspase is critically involved in 6-hydroxydopamine (6-OHDA)-mediated neurodegeneration. Here, we specifically attempted to examine whether and how these death signaling pathways may be linked to Bax translocation and oligomerization. We found that 6-OHDA treatment triggered translocation and oligomerization of Bax onto the mitochondria in MN9D dopaminergic neuronal cells. These events preceded cytochrome c release into the cytosol. Cross-linking assay revealed that co-treatment with a ROS scavenger or a pan-caspas... Apoptosis journals http://www.medworm.com/rss/comments.php?id=5017857 Fri, 08 Jul 2011 06:36:58 +0100 5017857 Elevated transcription of the p53 gene in early S-phase leads to a rapid DNA-damage response during S-phase of the cell cycle http://www.medworm.com/index.php?rid=4983308&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F126v3t71741646v1%2F Abstract  p53 induces the transcription of genes that negatively regulate progression of the cell cycle in response to DNA damage or other cellular stressors, and thus participates in maintaining genome stability. Under stress conditions, p53 must be activated to prohibit the replication of cells containing damaged DNA. However, in normal, non-stressed cells, p53 activity must be inhibited. Previous studies have demonstrated that p53 transcription is activated before or during early S-phase in cells progressing from G0/G1 into S-phase. Since this is not what would be predicted from a gene involved in growth arrest and apoptosis, in this study, we provide evidence that this induction occurs to provide sufficient p53 mRNA to ensure a rapid response to DNA damage before exitin... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4983308 Mon, 27 Jun 2011 18:11:45 +0100 4983308 Withaferin A induces apoptosis in human melanoma cells through generation of reactive oxygen species and down-regulation of Bcl-2 http://www.medworm.com/index.php?rid=4983309&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fql72u92v51646032%2F Abstract  A high resistance and heterogeneous response to conventional anti-cancer chemotherapies characterize malignant cutaneous melanoma, the most aggressive and deadly form of skin cancer. Withaferin A (WFA), a withanolide derived from the medicinal plant Withania somnifera, has been reported for its anti-tumorigenic activity against various cancer cells. For the first time, we examined the death-inducing potential of WFA against a panel of four different human melanoma cells and investigated the cellular mechanisms involved. WFA induces apoptotic cell death with various IC50 ranging from 1.8 to 6.1 μM. The susceptibility of cells toward WFA-induced apoptosis correlated with low Bcl-2/Bax and Bcl-2/Bim ratios. In all cell lines, the apoptotic process triggered by WF... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4983309 Mon, 27 Jun 2011 18:11:43 +0100 4983309 ARTS binds to a distinct domain in XIAP-BIR3 and promotes apoptosis by a mechanism that is different from other IAP-antagonists http://www.medworm.com/index.php?rid=4967612&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F73288u17358n8874%2F In this study, we show that ARTS and XIAP bind directly to each other, as recombinant ARTS and XIAP proteins co-immunoprecipitate together. We also show that over expression of ARTS alone is sufficient to induce a strong down-regulation of XIAP protein levels and that this reduction occurs through the ubiquitin proteasome system (UPS). Using various deletion and mutation constructs of XIAP we show that ARTS specifically binds to the BIR3 domain in XIAP. Moreover, we found that ARTS binds to different sequences in BIR3 than other IAP antagonists such as SMAC/Diablo. Computational analysis comparing the location of the putative ARTS interface in BIR3 with the known interfaces of SMAC/Diablo and caspase 9 support our results indicating that ARTS interacts with residues in BIR3 that are... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4967612 Wed, 22 Jun 2011 06:04:29 +0100 4967612 Insulin receptor signaling activated by penta-O-galloyl-α-d-glucopyranose induces p53 and apoptosis in cancer cells http://www.medworm.com/index.php?rid=4951360&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb54153416m21248n%2F Abstract  p53 is essential for cell cycle arrest and apoptosis induction while insulin receptor (IR) signaling is important for cell metabolism and proliferation and found upregulated in cancers. While IR has recently been found to be involved in apoptosis, p53 induction or apoptosis mediated through IR signaling activation has never been documented. Here, we report that the IR signaling pathway, particularly the IR-MEK pathway, mediates biological and biochemical changes in p53 and apoptosis in tumor cells. Specifically, natural compound penta-O-galloyl-α-d-glucopyranose (α-PGG), a previously characterized IR signaling activator, induced apoptosis in RKO cells without significantly affecting its normal counterpart FHC cells. α-PGG induced apoptosis in RKO cells through p... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4951360 Tue, 14 Jun 2011 05:55:53 +0100 4951360 Role of Bim in apoptosis induced in H460 lung tumor cells by the spindle poison Combretastatin-A4 http://www.medworm.com/index.php?rid=4951361&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftg071j3559v70m0q%2F Abstract  The BH3-only Bcl-2 subfamily member Bim is a well known apoptosis promoting protein. However, the mechanisms upstream of mitochondrion membrane permeability by which Bim is involved in apoptosis have been poorly investigated, particularly in response to agents capable of interfering with the cytoskeleton architecture and arresting cells in mitosis. Based on the observation that Bim is sequestered on the microtubule-array by interaction with the light chain of dynein, we have investigated upon depolymerisation, whether Bim could be involved in the commitment of apoptosis. With this purpose H460 Non Small Lung Cancer Cells (NSLC) were treated with the microtubule damaging agent combretastatin-A4 (CA-4) (7.5 nM; 8–48 h), and various parameters were investi... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4951361 Tue, 14 Jun 2011 05:55:52 +0100 4951361 HDAC inhibitors potentiate the apoptotic effect of enzastaurin in lymphoma cells http://www.medworm.com/index.php?rid=4932315&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9r724714x8523631%2F Abstract  Enzastaurin is an investigational PKCβ inhibitor that has growth inhibitory and pro-apoptotic effects in both B and T-cell lymphomas. We investigated the cytotoxicity and mechanisms of cell death of the combination of enzastaurin and low concentrations of histone deacetylase (HDAC) inhibitors in B-cell and T-cell lymphoma cell lines and primary lymphoma/leukemia cells. Combined enzastaurin/suberoylanilide hydroxamic acid treatment synergistically induced apoptosis in diffuse large B-cell lymphoma and T-cell lymphoma cell lines, and primary lymphoma/leukemia samples. Similarly, combined treatment of B-cell-like lymphoma cells with enzastaurin and two different HDAC inhibitors, valproic acid and (2E,4E)-6-(4-chlorophenylsulfanyl)-2,4-hexadienoic acid hydroxyamide sy... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4932315 Sat, 11 Jun 2011 06:33:12 +0100 4932315 Low doses of the novel caspase-inhibitor GS-9450 leads to lower caspase-3 and -8 expression on peripheral CD4+ and CD8+ T-cells http://www.medworm.com/index.php?rid=4932317&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg0n172w582p0r132%2F This study evaluated the effects of GS-9450 on peripheral T-cell apoptosis in chronic HCV-infected patients. As sub study of the GS-US-227-0102, a double-blind, placebo-controlled phase 2a trial evaluating the safety and tolerability of GS-9450, apoptosis of peripheral CD4+ and CD8+ T-cells was measured using activated caspase-3, activated caspase-8 and CD95 (Fas). Blood samples were drawn at baseline, day 14 after therapy and at 5 weeks off-treatment follow-up in the first cohort of 10 mg. In contrast to the placebo-treated patients, GS-9450 caused a median of 46% decrease in ALT-values from baseline to day 14 in all treated patients (median of 118–64 U/l) rising again to a median of 140 U/l (19%) at 5 weeks off-treatment follow-up. In GS9450-treated patie... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4932317 Sat, 11 Jun 2011 06:33:10 +0100 4932317 Defect in mevalonate pathway induces pyroptosis in Raw 264.7 murine monocytes http://www.medworm.com/index.php?rid=4932316&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq7639351607241q9%2F In this study we investigated the effect of ALD + LPS on monocyte cell line (Raw 264.7) death. ALD strongly augmented LPS-induced programmed cell death (PCD) as well as IL-1β secretion in Raw murine monocytes, whereas necrosis was rather unaffected. ALD + LPS induced caspase-3 activation. Inhibition of IL-1β stimulation partially restored cell viability. These findings suggest that the inhibition of mevalonate pathway, together with a bacterial stimulus, induce a PCD partly sustained by the caspase-3-related apoptosis and partly by caspase-1-associated pyroptosis. The involvement of pyroptosis is a novel hit in our cell model and opens discussions about its role in inflammatory cells with chemical or genetic inhibition of mevalonate pathway. Content Type Jo... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4932316 Sat, 11 Jun 2011 06:33:10 +0100 4932316 The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells http://www.medworm.com/index.php?rid=4932318&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8235h37363774q6t%2F In this study, we focused on elucidating the cytotoxic mechanism of naphthazarin in A549 non-small cell lung carcinoma cells. Naphthazarin reduced the A549 cell viability considerably with an IC50 of 16.4 ± 1.6 μM. Naphthazarin induced cell death in a dose- and time-dependent manner by activating apoptosis and autophagy pathways. Specifically, we found naphthazarin inhibited the PI3K/Akt cell survival signalling pathway, measured by p53 and caspase-3 activation, and PARP cleavage. It also resulted in an increase in the ratio of Bax/Bcl2 protein levels, indicating activation of the mitochondrial apoptotic pathway. Similarly naphthazarin triggered LC3II expression and induced autophagic flux in A549 cells. We demonstrated further that naphthazarin is a microtubule inhi... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4932318 Sat, 11 Jun 2011 06:33:08 +0100 4932318 Singapore grouper iridovirus, a large DNA virus, induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling http://www.medworm.com/index.php?rid=4920020&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg6m5619185k4860k%2F Abstract  Virus induced cell death, including apoptosis and nonapoptotic cell death, plays a critical role in the pathogenesis of viral diseases. Singapore grouper iridovirus (SGIV), a novel iridovirus of genus Ranavirus, causes high mortality and heavy economic losses in grouper aquaculture. Here, using fluorescence microscopy, electron microscopy and biochemical assays, we found that SGIV infection in host (grouper spleen, EAGS) cells evoked nonapoptotic programmed cell death (PCD), characterized by appearance of cytoplasmic vacuoles and distended endoplasmic reticulum, in the absence of DNA fragmentation, apoptotic bodies and caspase activation. In contrast, SGIV induced typical apoptosis in non-host (fathead minnow, FHM) cells, as evidenced by caspase activation and DNA ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4920020 Wed, 08 Jun 2011 15:46:09 +0100 4920020 Plasminogen K5 activates mitochondrial apoptosis pathway in endothelial cells by regulating Bak and Bcl-xL subcellular distribution http://www.medworm.com/index.php?rid=4920021&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0ln371m5164711g7%2F Abstract  Plasminogen Kringle 5(K5) is a proteolytic fragment of plasminogen, which displays potent anti-angiogenic activities. K5 has been shown to induce apoptosis in proliferating endothelial cells; however the exact mechanism has not been well explored. The present study was designed to elucidate the possible molecular mechanism of K5-induced endothelial cell apoptosis. Our results showed that K5 inhibited basic fibroblast growth factors activated in human umbilical vein endothelial cells (HUVECs), indicating proliferation in a dose-dependent manner and induced endothelial cell death via apoptosis. K5 exposure activated caspase 7, 8 and 9. These results suggested that both the intrinsic mitochondrial apoptosis pathway and extrinsic pathway might be involved in K5-induce... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4920021 Wed, 08 Jun 2011 15:46:08 +0100 4920021 The pro-apoptotic BH3-only protein Bid is dispensable for development of insulitis and diabetes in the non-obese diabetic mouse http://www.medworm.com/index.php?rid=4920022&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2l37257624311361%2F Abstract  Type 1 diabetes is caused by death of insulin-producing pancreatic beta cells. Beta-cell apoptosis induced by FasL may be important in type 1 diabetes in humans and in the non-obese diabetic (NOD) mouse model. Deficiency of the pro-apoptotic BH3-only molecule Bid protects beta cells from FasL-induced apoptosis in vitro. We aimed to test the requirement for Bid, and the significance of Bid-dependent FasL-induced beta-cell apoptosis in type 1 diabetes. We backcrossed Bid-deficient mice, produced by homologous recombination and thus without transgene overexpression, onto a NOD genetic background. Genome-wide single nucleotide polymorphism analysis demonstrated that diabetes-related genetic regions were NOD genotype. Transferred beta cell antigen-specific CD8+ T cells... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4920022 Sun, 05 Jun 2011 05:45:43 +0100 4920022 Defective nuclear translocation of stress-activated signaling in senescent diploid human fibroblasts: a possible explanation for aging-associated apoptosis resistance http://www.medworm.com/index.php?rid=4901307&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F88552k124225j052%2F Abstract  In order to study the nature of aging-dependent apoptosis resistance, we compared the activation pattern of mitogen-activated protein kinases (MAPK) in response to three different stress modalities: hydrogen peroxide (H2O2), staurosporine, and thapsigargin. We observed the agonist-specific activation pattern of MAP kinases in human diploid fibroblasts (HDFs). When young HDFs were treated with PD98059, a specific inhibitor of extracellular signal-regulated kinase (ERK), H2O2-induced apoptosis was blocked, whereas staurosporine-induced apoptosis was inhibited by treatment with SB203580, a specific inhibitor of p38. In addition, the levels of anti-apoptotic protein Bcl-2 (B-cell lymphoma protein-2) were restored by PD98059 or SB239063 in cells treated with H2O2 or stau... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4901307 Wed, 01 Jun 2011 05:48:54 +0100 4901307 Pro-apoptotic cell death genes, hid and reaper, from the tephritid pest species, Anastrepha suspensa http://www.medworm.com/index.php?rid=4901308&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0xr0403l8h00182k%2F Abstract  Pro-apoptotic proteins from the reaper, hid, grim (RHG) family are primary regulators of programmed cell death in Drosophila due to their antagonistic effect on inhibitor of apoptosis (IAP) proteins, thereby releasing IAP-inhibition of caspases that effect apoptosis. Using a degenerate PCR approach to conserved domains from the 12 Drosophila species, we have identified the first reaper and hid orthologs from a tephritid, the Caribfly Anastrepha suspensa. As-hid is the first identified non-drosophilid homolog of hid, and As-rpr is the second non-drosophilid rpr homolog. Both genes share more than 50% amino acid sequence identity with their Drosophila homologs, suggesting that insect pro-apoptotic peptides may be more conserved than previously anticipated. Importantly, ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4901308 Wed, 01 Jun 2011 05:48:53 +0100 4901308 Shogaols at proapoptotic concentrations induce G2/M arrest and aberrant mitotic cell death associated with tubulin aggregation http://www.medworm.com/index.php?rid=4861255&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg02666857w465gh2%2F In this study, a series of shogaols with different side chain lengths (4-, 6-, 8- and 10-shogaol) was synthesized and evaluated for antiproliferative activity in HCT 116 colon carcinoma and SH-SY5Y neuroblastoma cells. 4- and 6-shogaol were identified as lead compounds possessing the strongest antiproliferative activity. In the soft agar assay, the lead shogaols displayed dose-dependent inhibition on cancer cell colony formation under anchorage-independent conditions. Using HCT 116 as the selected cancer cell line, the molecular events linking shogaols-induced G2/M cell cycle arrest to apoptosis characterized by caspase 3 and PARP cleavage were investigated. At sublethal concentrations, the halt at G2/M phase was alleviated along time and cells survived. Conversely, proapoptotic conc... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4861255 Fri, 20 May 2011 05:57:01 +0100 4861255 Hydroxyl radical mediates cisplatin-induced apoptosis in human hair follicle dermal papilla cells and keratinocytes through Bcl-2-dependent mechanism http://www.medworm.com/index.php?rid=4839742&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5316283285123747%2F Abstract  Induction of massive apoptosis of hair follicle cells by chemotherapy has been implicated in the pathogenesis of chemotherapy-induced alopecia (CIA), but the underlying mechanisms of regulation are not well understood. The present study investigated the apoptotic effect of cisplatin in human hair follicle dermal papilla cells and HaCaT keratinocytes, and determined the identity and role of specific reactive oxygen species (ROS) involved in the process. Treatment of the cells with cisplatin induced ROS generation and a parallel increase in caspase activation and apoptotic cell death. Inhibition of ROS generation by antioxidants inhibited the apoptotic effect of cisplatin, indicating the role of ROS in the process. Studies using specific ROS scavengers further showe... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4839742 Sat, 14 May 2011 16:02:33 +0100 4839742 Inhibition of cellular FLICE-like inhibitory protein abolishes insensitivity to interferon-α and death receptor stimulation in resistant variants of the human U937 cell line http://www.medworm.com/index.php?rid=4839743&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb724143115m28371%2F Abstract  Type I interferons constitute a family of pleiotropic cytokines that have a key role in both adaptive and innate immunity. The interferon signalling pathways mediate transcriptional regulation of hundreds of genes, which result in mRNA degradation, decreased protein synthesis, cell cycle inhibition and induction of apoptosis. To elucidate regulatory networks important for interferon induced cell death, we generated interferon resistant U937 cells by selection in progressively increasing concentrations of interferon-α (IFN-α). The results show that IFN-α activates the death receptor signalling pathway and that IFN resistance was associated with cross-resistance to several death receptor ligands in a manner similar to previously described Fas resistant U937 cell ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4839743 Thu, 12 May 2011 19:28:56 +0100 4839743 YAP accelerates Aβ25–35-induced apoptosis through upregulation of Bax expression by interaction with p73 http://www.medworm.com/index.php?rid=4839744&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh81110777tx14w20%2F Abstract  Accumulation of amyloid-β-peptide (Aβ) in the brain is considered as a pathological hallmark of Alzheimer’s disease (AD). Previous studies show that p73 is vital for mediating the pathogenic process of AD. Yes-associated protein (YAP) has been shown to positively regulate p73 in promoting apoptosis induced by anti-cancer agents. However, the functional role of YAP and potential relationship between YAP and p73 in AD are unknown. In the present study, we found that YAP accelerated apoptosis in response to Aβ25–35 and the nuclear translocation of YAP was involved in cellular signals that regulated the apoptosis. Aβ25–35 induced YAP translocation from cytoplasm to nucleus accompanied with the increased phosphorylation on Y357, resulting in the enhancement of... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4839744 Thu, 12 May 2011 19:28:52 +0100 4839744 Cellular localization of human p53 expressed in the yeast Saccharomyces cerevisiae: effect of NLSI deletion http://www.medworm.com/index.php?rid=4811970&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl71476m7x605vt58%2F In conclusion, our results provide evidence that the human wtp53 is active in S. cerevisiae probably through dependent and independent transcriptional mechanisms leading to cell death. The deletion of the NLSI sequence decreases p53 nuclear translocation as well as its mitochondrial localization and consequently its effect on yeast growth. Content Type Journal ArticlePages 1-11DOI 10.1007/s10495-011-0607-zAuthors Salma Abdelmoula-Souissi, University of Sfax, Laboratoire de Valorisation de la Biomasse et Production de Protéines chez les Eucaryotes, Centre de Biotechnologie de Sfax, Route Sidi Mansour, BP 1177, 3018 Sfax, TunisiaAgnès Delahodde, Université Paris-Sud, Institut de Génétique et Microbiologie, CNRS UMR8621, F-91405 Orsay, FranceMonique Bolotin-Fukuhara, Université... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4811970 Sat, 07 May 2011 15:44:30 +0100 4811970 Erratum to: Gender differences in apoptotic signaling in heart failure due to volume overload http://www.medworm.com/index.php?rid=4811971&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4930626053204760%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s10495-011-0598-9Authors Melissa R. Dent, Department of Physiology, Faculty of Medicine, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, MB R2H 2A6, CanadaParamjit S. Tappia, Department of Physiology, Faculty of Medicine, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, MB R2H 2A6, CanadaNaranjan S. Dhalla, Department of Physiology, Faculty of Medicine, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, MB R2H 2A6, Canada Journal ApoptosisOnline ISSN 1573-675XPrint ISSN 1360-8185 (Source: Apoptosis) Apoptosis journals http://www.medworm.com/rss/comments.php?id=4811971 Sat, 07 May 2011 15:44:28 +0100 4811971 Cryptotanshinone enhances TNF-α-induced apoptosis in chronic myeloid leukemia KBM-5 cells http://www.medworm.com/index.php?rid=4770690&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F44815l6872242057%2F Abstract  Cryptotanshinone is a biologically active compound from the root of Salvia miltiorrhiza. In the present study, we investigated the molecular mechanisms by which cryptotanshinone is in synergy with tumor necrosis factor-alpha (TNF-α) for the induction of apoptosis in human chronic myeloid leukemia (CML) KBM-5 cells. The co-treatment of cryptotanshinone with TNF-α reduced the viability of the cells [combination index (CI) < 1]. Concomitantly, the co-treatment of cryptotanshinone and TNF-α elicited apoptosis, manifested by enhanced the number of terminal deoxynucleotide transferase-mediated dUTP-nick-end labeling (TUNEL)-positive cells, the sub-G1 cell populations, and the activation of caspase-8 and -3, in comparison with the treatment with either dru... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4770690 Mon, 25 Apr 2011 16:39:15 +0100 4770690 Apoptosis induced by overall metabolic stress converges on the Bcl-2 family proteins Noxa and Mcl-1 http://www.medworm.com/index.php?rid=4752951&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7hr20718545812v4%2F In conclusion, Noxa functions in a specific apoptotic pathway that integrates overall nutrient stress, independent from attenuated PI3K/PKB signaling and without clear involvement of autophagy. Content Type Journal ArticlePages 1-14DOI 10.1007/s10495-011-0599-8Authors Felix M. Wensveen, Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9, Room K0-144, 1105 AZ Amsterdam, The NetherlandsNuno L. Alves, Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9, Room K0-144, 1105 AZ Amsterdam, The NetherlandsIngrid A. M. Derks, Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9, Room K0-144, 1105 AZ Amsterdam, The NetherlandsKris A. Reedquist, Department of Clinical Immunology and Rheumatology, Academic Medical... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4752951 Fri, 22 Apr 2011 16:04:05 +0100 4752951 Matrix metalloproteinases and soluble Fas/FasL system as novel regulators of apoptosis in children and young adults on chronic dialysis http://www.medworm.com/index.php?rid=4752950&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ffx0l294355766336%2F Abstract  The system of membrane receptor Fas and its ligand FasL compose one of the main pathways triggering apoptosis. However, the role of their soluble forms has not been clarified yet. Although sFasL can be converted from the membrane-bound form by matrix metalloproteinases (MMPs), there are no data on relations between sFas/sFasL, MMPs and their tissue inhibitors (TIMPs) in patients on chronic dialysis—neither children nor adults. The aim of our study was to evaluate serum concentrations of sFas, sFasL, and their potential regulators (MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2), in children and young adults chronically dialyzed. Twenty-two children on automated peritoneal dialysis (APD), 19 patients on hemodialysis (HD) and 30 controls were examined. Serum concentrations o... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4752950 Fri, 22 Apr 2011 16:04:05 +0100 4752950 Transcriptional modulation of apoptosis regulators by roscovitine and related compounds http://www.medworm.com/index.php?rid=4744641&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F26887k4n1350r7g7%2F In conclusion, the increased expression of PUMA was not associated with apoptosis induction. On the contrary, mRNA and protein depletion of MCL-1 gene correlated the best with cell demise. Moreover, NOXA protein suffered a far minor decrease than MCL-1. Because of the selective neutralization of NOXA by MCL-1, we hypothesize that the disruption of this balance is a critical event in apoptosis induction by roscovitine and related compounds. Content Type Journal ArticlePages 1-11DOI 10.1007/s10495-011-0603-3Authors Xènia Garrofé-Ochoa, Molecular Pharmacology Group, Departament de Medicina Experimental, IRBLLEIDA-Universitat de Lleida, C/Montserrat Roig 2, 25008 Lleida, Catalunya, SpainAna M. Cosialls, Departament de Ciències Fisiològiques II, IDIBELL-Universitat de Barcelona, Ca... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4744641 Wed, 20 Apr 2011 06:08:41 +0100 4744641 Induction of lactadherin mediates the apoptosis of endothelial cells in response to advanced glycation end products and protective effects of grape seed procyanidin B2 and resveratrol http://www.medworm.com/index.php?rid=4744642&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F188r428pur116230%2F Abstract  One of characteristics of diabetes mellitus (DM) is endothelial cell (EC) dysfunction and apoptosis which contributes to the development of vasculopathy. Advanced glycation end products (AGEs) continuously produced in the setting of DM play an important role in causing EC dysfunction and apoptosis. However, the underlying molecular mechanism remains largely elusive. Lactadherin, a secreted glycoprotein of milk-fat globule, is expressed by multiple cell types of arterial wall including ECs. Our previous proteomic studies showed that the expression of lactadherin was significantly increased in the aorta of diabetic rats as compared with control rats and treatment with grape seed procyanidin extracts significantly inhibited the lactadherin expression in diabetic rats... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4744642 Wed, 20 Apr 2011 06:08:40 +0100 4744642 In vivo targeting of cell death using a synthetic fluorescent molecular probe http://www.medworm.com/index.php?rid=4744643&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ffw750353l2j5x551%2F Abstract  A synthetic, near-infrared, fluorescent probe, named PSS-794 was assessed for its ability to detect cell death in two animal models. The molecular probe contains a zinc(II)-dipicolylamine (Zn2+-DPA) affinity ligand that selectively targets exposed phosphatidylserine on the surface of dead and dying cells. The first animal model used rats that were treated with dexamethasone to induce thymic atrophy. Ex vivo fluorescence imaging and histological analysis of excised organs showed thymus uptake of PSS-794 was four times higher than a control fluorophore that lacked the Zn2+-DPA affinity ligand. In addition, the presence of PSS-794 produced a delayed and higher build up of dead and dying cells in the rat thymus. The second animal model employed focal beam radiation to ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4744643 Sat, 16 Apr 2011 05:53:37 +0100 4744643 Inhibition of cathepsin L lowers the apoptotic threshold of glioblastoma cells by up-regulating p53 and transcription of caspases 3 and 7 http://www.medworm.com/index.php?rid=4722978&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr3w7454t43523l48%2F Abstract  Despite all the progress in cancer treatment, glioblastoma, the most malignant tumor of the central nervous system, remains a terminal disease and new therapeutic approaches are urgently needed. A combination of chemotherapy with modifications that lower the apoptotic threshold of cancer cells could be effective. Cathepsin L inhibition was suggested as one of such modifications but the mechanism of cathepsin L anti-apoptotic activity is largely unknown. In the present study we show that, in U87 glioblastoma cells, cathepsin L is present in the nucleus and regulates the transcription of effector caspases 3 and 7. In cells with low cathepsin L expression, p53 and prohibitin—transcription factors that regulate caspase 7 expression—accumulate in the nuclei. The im... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4722978 Tue, 12 Apr 2011 05:59:08 +0100 4722978 Lentiviral shRNA silencing of CHOP inhibits apoptosis induced by cyclic stretch in rat annular cells and attenuates disc degeneration in the rats http://www.medworm.com/index.php?rid=4708670&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4646tx6540x6h352%2F In conclusion, a novel lentiviral vector expressing CHOP shRNA efficiently inhibits apoptosis in rat AF cells by silencing CHOP expression. In a rat model, intradiscal injection of CHOP shRNA induces the suppression of disc degeneration. The therapeutic effects of lentiviral CHOP shRNA should be further explored. Content Type Journal ArticlePages 1-12DOI 10.1007/s10495-011-0596-yAuthors Yue-Hui Zhang, Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092 ChinaChang-Qing Zhao, Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092 ChinaLei-Sheng Jiang, Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaoto... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4708670 Fri, 08 Apr 2011 16:58:43 +0100 4708670 Apoptosis induced by an antagonist peptide against HPV16 E7 in vitro and in vivo via restoration of p53 http://www.medworm.com/index.php?rid=4696043&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F14h486k24076165l%2F Abstract  Human papilloma virus type 16 (HPV16) E7 is a viral oncoprotein that is believed to play a major role in cervical neoplasia. A novel antagonist peptide against HPV16 E7 was previously selected by phage display screening and the selected peptide was found to have anti-tumor efficacy against HPV16-positive cervical carcinoma through induction of cell cycle arrest. In the current study, to further elucidate the mechanisms of the antagonist peptide, the effects of the peptide on apoptosis are investigated by RT-PCR, Western blotting, MTT assay, TUNEL staining, Annexin V apoptosis assay, flow cytometry, and animal experiments. The antagonist peptide showed obvious anti-tumor efficacy through apoptosis induction, both in HPV16-positive cervical cancer cell lines and tum... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4696043 Thu, 07 Apr 2011 17:09:42 +0100 4696043 Trichostatin A sensitizes HBx-expressing liver cancer cells to etoposide treatment http://www.medworm.com/index.php?rid=4692518&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl52544r445811457%2F In this study, we showed that etoposide treatment activated caspase-8 and caspase-3, leading to cleavages of p53, Bid and PARP, which subsequently induced apoptosis. Furthermore, p53 and Bid were accumulated in cytoplasm following etoposide treatment. However, HBx significantly attenuated etoposide-induced cell death. In HBx-expressing cells, despite the translocation of p53 and Bid to cytoplasm, the activation of caspases was inhibited. Furthermore, the phosphorylation of extracellular-signal-regulated kinase (ERK) was markedly increased in HBx-expressing cells. Moreover, the pretreatment with trichostatin A (TSA, a histone deacetylase inhibitor) or TSA in combination with etoposide significantly sensitized HCC cells to apoptosis by inhibiting ERK phosphorylation, reactivating caspa... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4692518 Tue, 05 Apr 2011 16:57:11 +0100 4692518 Involvement of the mitogen-activated protein kinase pathway in soft-shelled turtle iridovirus-induced apoptosis http://www.medworm.com/index.php?rid=4652008&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F93514m8pr760r4q2%2F Abstract  Iridoviruses are large DNA viruses that infect invertebrates and poikilothermic vertebrates, and result in significant economic losses in aquaculture production, and drastic declines in amphibian populations. Soft-shelled turtle iridovirus (STIV) is the causative agent of severe systemic diseases in farm-raised soft-shelled turtles (Trionyx sinensis). In the present study, the mechanisms of STIV-induced cell death and the roles of the mitogen-activated protein kinase (MAPK) signaling pathway were investigated. STIV infection evoked typical apoptosis in fish cells, as demonstrated by the formation of apoptotic bodies, positive terminal deoxynucleotidyl transferase-mediated nicked-end labeling, and caspase-3 activation. The translocation of cytochrome c from mitochon... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4652008 Sun, 27 Mar 2011 05:48:51 +0100 4652008 Nonlinear regulation of commitment to apoptosis by simultaneous inhibition of Bcl-2 and XIAP in leukemia and lymphoma cells http://www.medworm.com/index.php?rid=4641704&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp48011v8r1871844%2F This study justifies further ex vivo and animal studies on the potential of the treatment of leukemia and lymphoma with a combination of BH3 mimetics and XIAP inhibitors. Content Type Journal ArticlePages 1-8DOI 10.1007/s10495-011-0593-1Authors Joanna Skommer, School of Biological Sciences, University of Auckland, 3a Symonds Street, Auckland, 1142 New ZealandSomkanya C. Das, Department of Biomedical Engineering, University of California, Davis, CA 95616, USAArjun Nair, Department of Biomedical Engineering, University of California, Davis, CA 95616, USAThomas Brittain, School of Biological Sciences, University of Auckland, 3a Symonds Street, Auckland, 1142 New ZealandSubhadip Raychaudhuri, Department of Biomedical Engineering, University of California, Davis, CA 95616, USA Jo... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4641704 Fri, 25 Mar 2011 18:50:53 +0100 4641704 PI3 Kinase inhibition on TRAIL-induced apoptosis correlates with androgen-sensitivity and p21 expression in prostate cancer cells http://www.medworm.com/index.php?rid=4641705&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv300860372433273%2F Abstract  TNF-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in many types of cancer cells. TRAIL is considered a therapeutic target, therefore, it was of interest to examine molecular mechanisms that may modulate sensitivity to TRAIL signaling in prostate cancer cells. LNCaP cells were found to be relatively resistant to TRAIL induced cell death while PC3 cells were sensitive. PI3-kinase (PI3 K) inhibitors were able to render LNCaP cells sensitive to TRAIL but conferred resistance to PC3 cells. PI3 K inhibitors were associated with an increase in p21waf1, cip1 expression in PC3 cells where as p21 decreases in LNCaP cells suggesting that p21 may impart TRAIL resistance. Since androgen receptor (AR) signaling can be modulated by AKT, and p21 is an AR... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4641705 Fri, 25 Mar 2011 06:00:09 +0100 4641705 Synthetic glycosidated phospholipids induce apoptosis through activation of FADD, caspase-8 and the mitochondrial death pathway http://www.medworm.com/index.php?rid=4641706&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc2753828483155h2%2F In conclusion, Ino-C2-PAF and Glc-PAF trigger a CD95/Fas ligand- and receptor-independent atypical DISC that relies on the intrinsic apoptotic pathway via the ER and the mitochondria. Content Type Journal ArticlePages 1-16DOI 10.1007/s10495-011-0592-2Authors Clarissa von Haefen, Department of Anaesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, GermanyJana Wendt, Department of Haematology, Oncology and Tumor Immunology, University Medical Center Charité, Campus Buch, Berlin, GermanyGeo Semini, Institute of Biochemistry, Campus Virchow Klinikum, University Medical Center Charité, Berlin, GermanyMarco Sifringer, Department of Anaesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4641706 Fri, 25 Mar 2011 06:00:08 +0100 4641706 Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure http://www.medworm.com/index.php?rid=4621472&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9114180504373j83%2F This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15–21 (E15–E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocycline. Pups were killed on postnatal day 15 (P15). Additional pregnant dams received twice daily IP injections of cocaine (from E15–E21) + oral administration of a relatively higher (37.5 mg/kg BW) dose of minocycline. Minocycline treatment continued from E1... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4621472 Sat, 19 Mar 2011 16:57:22 +0100 4621472 Antiapoptotic effects of roscovitine on camptothecin-induced DNA damage in neuroblastoma cells http://www.medworm.com/index.php?rid=4621473&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgw762448885q5838%2F Abstract  In the present study dopaminergic neuroblastoma B65 cells were exposed to Camptothecin (CPT) (0.5–10 μM), either alone or in the presence of roscovitine (ROSC). The results show that CPT induces apoptosis through the activation of ataxia telangiectasia mutated (ATM)-induced cell-cycle alteration in neuroblastoma B65 cells. The apoptotic process is mediated through the activation of cystein proteases, namely calpain/caspases. However, whereas a pan-caspase inhibitor, zVADfmk, inhibited CPT-mediated apoptosis, a calpain inhibitor, calpeptin, did not prevent cell death. Interestingly, CPT also induces CDK5 activation and ROSC (25 μM) blocked CDK5, ATM activation and apoptosis (as measured by caspase-3 activation). By contrast, selective inhibition of ATM... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4621473 Sat, 19 Mar 2011 16:57:20 +0100 4621473 PARP inhibition prevents oxidative injury of bladder induced by acute urinary retention and subsequent emptying http://www.medworm.com/index.php?rid=4614691&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7x24g6nr4h1685hw%2F Abstract  It has been demonstrated that increases in poly(ADP-ribose) polymerase (PARP) activity causes damage to several organs under ischemia/reperfusion (I/R) conditions. The aims of this study were to investigate whether inhibition of PARP could suppress apoptosis in the bladder following acute urinary retention (AUR) and subsequent bladder emptying. Twelve-week-old male Sprague Dawley rats were divided into a control group, saline treated group, and 3-aminobenzamide (3-AB, a specific PARP inhibitor)-treated group. Sixty minutes after the administration of saline and 3-AB, the saline and 3-AB-treated groups had 60 min of over-distension and followed by 2 h of drainage. The degree of bladder apoptosis, levels of malondialdehyde (MDA), ATP and nicotinamide a... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4614691 Thu, 17 Mar 2011 18:33:10 +0100 4614691 Conversation between apoptosis and autophagy: “Is it your turn or mine?” http://www.medworm.com/index.php?rid=4599915&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc7433k2j5118715p%2F Abstract  Drug resistance of cancer cells is often correlated with apoptosis evasion; however, an active involvement of autophagy in this scenario has been recently proposed, based on the evidence that autophagy could exert a protective role toward the activation of apoptosis in cancer cells. In this review, we briefly review the basic features of apoptosis, and we describe in details the molecular patterns of autophagy, with a special emphasis on its still controversial physiological function(s). The crucial factors governing the cross talk between autophagy and apoptosis will be illustrated. Content Type Journal ArticlePages 1-13DOI 10.1007/s10495-011-0589-xAuthors Vincenzo Giansanti, IGM-CNR, Via Abbiategrasso 207, 27100 Pavia, ItalyAlicia Torriglia, Université Pie... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4599915 Mon, 14 Mar 2011 16:56:05 +0100 4599915 Apoptotic regulation of epithelial cellular extrusion http://www.medworm.com/index.php?rid=4580621&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd7502357114822tt%2F Abstract  Cellular extrusion is a mechanism that removes dying cells from epithelial tissues to prevent compromising their barrier function. Extrusion occurs in all observed epithelia in vivo and can be modeled in vitro by inducing apoptosis in cultured epithelial monolayers. We established that actin and myosin form a ring that contracts in the surrounding cells that drives cellular extrusion. It is not clear, however, if all apoptotic pathways lead to extrusion and how apoptosis and extrusion are molecularly linked. Here, we find that both intrinsic and extrinsic apoptotic pathways activate cellular extrusion. The contraction force that drives cellular extrusion requires caspase activity. Further, necrosis does not trigger the cellular extrusion response, but instead necr... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4580621 Fri, 11 Mar 2011 18:06:37 +0100 4580621 Toxoplasma gondii Dense Granule Antigen 1 stimulates apoptosis of monocytes through autocrine TGF-β signaling http://www.medworm.com/index.php?rid=4577744&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg64n67304px55007%2F Abstract  Monocyte/macrophages represent the first line of defense against protozoan parasites. Different mechanisms of monocyte suppression by Toxoplasma gondii that sustain parasite invasion and persistence have been described, including apoptosis. In the present study, we investigated the effect of microbial excretory–secretory polypeptides, namely the microneme protein MIC3 and the dense granule antigen GRA1, on apoptosis of monocytes from patients with congenital toxoplasmosis and healthy individuals. We found that GRA1 but not MIC3 could induce apoptosis of monocytes, observing the effect in samples from both Toxoplasma-infected and uninfected individuals, thus ruling out involvement of mechanisms of apoptosis linked to adaptive immunity or a cellular context related... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4577744 Wed, 09 Mar 2011 16:48:33 +0100 4577744 Local kallikrein–kinin system is involved in podocyte apoptosis under diabetic conditions http://www.medworm.com/index.php?rid=4559360&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff04941254t08674k%2F This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10−7 mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10−8 mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor ex... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4559360 Fri, 04 Mar 2011 11:04:15 +0100 4559360 ClC-3 chloride channel prevents apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells through mitochondria dependent pathway http://www.medworm.com/index.php?rid=4559361&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw3751hgx82058w48%2F Abstract  ClC-3 Cl− channel plays an important role in cell volume regulation and cell cycle. In vascular smooth muscle cells, we have found that ClC-3 was involved in ET-1 induced cell proliferation. The present study was designed to further investigate the role of ClC-3 Cl− channel in H2O2-induced apoptosis and its underlying mechanisms in rat basilar arterial smooth muscle cell (BASMCs). By using ClC-3 cDNA and small interference RNA (siRNA) transfection strategy, it was found that overexpression of ClC-3 significantly decreased the apoptotic rate of H2O2-treated BASMCs and increased the cell viability, whereas silencing of ClC-3 with siRNA produced opposite effects and increased the apoptotic rate. ClC-3 overexpression decreased cytochrome C release and caspase-3 act... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4559361 Fri, 04 Mar 2011 11:04:12 +0100 4559361 Characterization of dequalinium as a XIAP antagonist that targets the BIR2 domain http://www.medworm.com/index.php?rid=4511658&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fxm45135052573643%2F Abstract  Inhibitor of apoptosis proteins (IAPs) regulate the activity of caspases in apoptosis. The human X chromosome-encoded IAP (XIAP) is one of the more potent members of the IAP family and it has been described as a central regulator of apoptosis. Thus, molecules that inhibit XIAP could offer therapeutic opportunities to treat unwanted apoptosis inhibition. In the present study we have applied the selective optimization of side activities (SOSA) approach to the discovery of XIAP inhibitors. In this sense, we have identified dequalinium hydrochloride (Dq) as an inhibitor of the XIAP/caspase-3 interaction both in vitro and in cellular assays. Content Type Journal ArticlePages 1-8DOI 10.1007/s10495-011-0582-4Authors Mar Orzáez, Laboratory of Peptide and Protein Ch... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4511658 Mon, 21 Feb 2011 17:07:22 +0100 4511658 P-glycoprotein enhances radiation-induced apoptotic cell death through the regulation of miR-16 and Bcl-2 expressions in hepatocellular carcinoma cells http://www.medworm.com/index.php?rid=4511659&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff652029r6067415h%2F Abstract  P-glycoprotein (Pgp), an efflux pump, was confirmed the first time to regulate the expressions of miR/gene in cells. Pgp is known to be associated with multidrug resistance. RHepG2 cells, the multidrug resistant subline of human hepatocellular carcinoma HepG2 cells, expressed higher levels of Pgp as well as miR-16, and lower level of Bcl-2 than the parental cells. In addition, RHepG2 cells were more radiation sensitive and showed more pronounced radiation-induced apoptotic cell death than the parental cells. Mechanistic analysis revealed that transfection with mdr1 specific antisense oligos suppressed radiation-induced apoptosis in HepG2 cells. On the other hand, ectopic mdr1 expression enhanced radiation-induced apoptosis in HepG2 cells, SK-HEP-1 cells, MiHa cells,... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4511659 Sat, 19 Feb 2011 18:26:09 +0100 4511659 Chk1 has an essential role in the survival of differentiated cortical neurons in the absence of DNA damage http://www.medworm.com/index.php?rid=4511660&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F70q11448q3p636h7%2F Abstract  Neuronal death in the central nervous system contributes to the development of age-related neurodegeneration. The ATR/Chk1 pathway appears to function neuroprotectively to prevent DNA damage induced by cytotoxic agents. Here, we examine the function of Chk1 on cell viability of cortical neurons in the absence of additional DNA damaging stimuli. The Chk1-specific inhibitor, UCN-01, and the ATR inhibitor, Caffeine, cause neuronal apoptosis in differentiated neurons in the absence of additional treatment, whereas inhibition of ATM or Chk2, does not. UCN-01 treatment increased the detection of γ-H2AX phosphorylation, DNA strand breaks, and an activated p53-dependent DNA damage response (DDR), suggesting that Chk1 normally helps to maintain genomic stability. UCN-01 t... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4511660 Sat, 19 Feb 2011 18:26:08 +0100 4511660 Interruption of the MEK/ERK signaling cascade promotes dihydroartemisinin-induced apoptosis in vitro and in vivo http://www.medworm.com/index.php?rid=4501113&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8uk708r0g2160h24%2F Abstract  Artemisinin, the active principle of the Chinese medicinal herb Artemisia annua, and its derivatives (i.e. dihydroartemisinin, DHA) were reported to exhibit anti-tumor activity both in vitro and in vivo. The purpose of the present study was to investigate the functional role of Mitogen-Activated Protein Kinase (MEK)/Extracellular signal-regulated protein Kinase (ERK) signaling cascade in dihydroartemisinin (DHA)-induced apoptosis in human leukemia cells in vitro and anti-leukemic activity in vivo. Human leukemia cells were treated with DHA in dose- and time-dependent manners, after which apoptosis, caspase activation, Mcl-1 expression, and cell signaling pathways were evaluated. Parallel studies were performed in AML and ALL primary human leukemia cells. In vivo ant... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4501113 Fri, 18 Feb 2011 16:54:22 +0100 4501113 Apoptotic microtubule network organization and maintenance depend on high cellular ATP levels and energized mitochondria http://www.medworm.com/index.php?rid=4469901&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F47h1021vl35l1h77%2F Abstract  Microtubule cytoskeleton is reformed during apoptosis, forming a cortical structure beneath plasma membrane, which plays an important role in preserving cell morphology and plasma membrane integrity. However, the maintenance of the apoptotic microtubule network (AMN) during apoptosis is not understood. In the present study, we examined apoptosis induced by camptothecin (CPT), a topoisomerase I inhibitor, in human H460 and porcine LLCPK-1α cells. We demonstrate that AMN was organized in apoptotic cells with high ATP levels and hyperpolarized mitochondria and, on the contrary, was dismantled in apoptotic cells with low ATP levels and mitochondrial depolarization. AMN disorganization after mitochondrial depolarization was associated with increased plasma membrane pe... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4469901 Thu, 10 Feb 2011 19:58:14 +0100 4469901 XZH-5 inhibits STAT3 phosphorylation and causes apoptosis in human hepatocellular carcinoma cells http://www.medworm.com/index.php?rid=4469902&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft1893171w7km8t57%2F In this study, we demonstrated that blocking STAT3 phosphorylation with STAT3 small molecule inhibitors SD-1029 and Stattic caused apoptosis in HCC cells. Then we characterized the inhibitory effects of a novel small molecule XZH-5 on STAT3 phosphorylation in HCC cell lines. XZH-5 reduced constitutive STAT3 phosphorylation at Tyr705 and the expression of STAT3 downstream genes. The inhibition of STAT3 in HCC cells resulted in the induction of apoptosis and reduction of colony forming ability. In addition, XZH-5 also inhibited IL-6-induced STAT3 phosphorylation, nuclear translocation and STAT3 DNA binding activity. In contrast, it had no effect on IFN-γ-induced STAT1 phosphorylation, indicating the more selective effects on STAT3. These results suggested that XZH-5 may serve as a lea... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4469902 Thu, 10 Feb 2011 19:58:10 +0100 4469902 Light- and sodium azide-induced death of RGC-5 cells in culture occurs via different mechanisms http://www.medworm.com/index.php?rid=4428444&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp4244634h5702104%2F Abstract  Previous studies have shown that light impinging on the retina in situ has the capacity to kill neuronal and non-neuronal cells in vitro by interacting directly with mitochondrial constituents. A number of fluorophores are associated with mitochondria which can potentially absorb different wave-lengths of light, including cytochrome oxidase. The aim of the present study was to compare the death mechanism of a light insult to RGC-5 cells in culture with that of sodium azide. Sodium azide’s main toxic action is in inhibiting the function of cytochrome oxidase in the mitochondrial electron transport chain. Our studies showed that light and sodium azide kill RGC-5 cells via different mechanisms although some similarities do occur. Both inducers of cell death caused ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4428444 Fri, 28 Jan 2011 20:42:49 +0100 4428444 The role of IAP antagonist proteins in the core apoptosis pathway of the mosquito disease vector Aedes aegypti http://www.medworm.com/index.php?rid=4418521&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F361p88p73l32391r%2F In this study, we characterized the roles of two IAP antagonists, Michelob_x (Mx) and IMP, in apoptosis in the yellow fever mosquito Aedes aegypti. Overexpression of Mx or IMP caused apoptosis in A. aegypti Aag2 cells, while silencing expression of mx or imp attenuated apoptosis. Addition of recombinant Mx or IMP, but not cytochrome c, to Aag2 cytosolic extract caused caspase activation. Consistent with this finding, AeIAP1 bound and inhibited both initiator and effector caspases from A. aegypti, and Mx and IMP competed with caspases for binding to AeIAP1. However, a difference was observed in the BIR domains responsible for Dronc binding by AeIAP1 versus DIAP1. These findings demonstrate that the mechanisms by which IAP antagonists regulate apoptosis are largely conserved between A. a... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4418521 Thu, 27 Jan 2011 17:40:05 +0100 4418521 CHOP deletion does not impact the development of diabetes but suppresses the early production of insulin autoantibody in the NOD mouse http://www.medworm.com/index.php?rid=4418522&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F264547j654378342%2F Abstract  C/EBP homologous protein (CHOP) has been proposed as a key transcription factor for endoplasmic reticulum (ER) stress-mediated β-cell death induced by inflammatory cytokines in vitro. However, the contribution of CHOP induction to the pathogenesis of type 1 diabetes is not yet clear. To evaluate the relevance of CHOP in the pathogenesis of type 1 diabetes in vivo, we generated CHOP-deficient non-obese diabetic (NOD.Chop −/−) mice. CHOP deficiency did not affect the development of insulitis and diabetes and apoptosis in β-cells. Interestingly, NOD.Chop −/− mice exhibited a delayed appearance of insulin autoantibodies compared to wild-type (wt) mice. Adoptive transfer with the diabetogenic, whole or CD8+-depleted splenocytes induced β-cell apoptosis and t... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4418522 Thu, 27 Jan 2011 17:40:04 +0100 4418522 Bufadienolide compounds sensitize human breast cancer cells to TRAIL-induced apoptosis via inhibition of STAT3/Mcl-1 pathway http://www.medworm.com/index.php?rid=4404936&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F44030x3382101142%2F Abstract  The death receptor ligand TRAIL is considered a promising candidate for cancer therapy because of its preferential toxicity to malignant cells. However its efficacy has been challenged by a number of resistance mechanisms. Therefore, agents that can overcome the resistance to enhance therapeutic efficacy of TRAIL are needed. In the current study, we found that bufalin, bufotalin and gamabufotalin, key members of bufadienolides isolated from a traditional Chinese medicine ChanSu, significantly potentiated human breast cancer cells with different status of ER-alpha to apoptosis induction of TRAIL, as evidenced by enhanced Annexin V/FITC positive cells (apoptotic cells), cytoplasmic histone-associated-DNA-fragments, membrane permeability transition (MPT), caspases ac... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4404936 Sat, 22 Jan 2011 20:14:52 +0100 4404936 An apoptosis targeted stimulus with nanosecond pulsed electric fields (nsPEFs) in E4 squamous cell carcinoma http://www.medworm.com/index.php?rid=4324701&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F21244405j84h7172%2F Abstract  Stimuli directed towards activation of apoptosis mechanisms are an attractive approach to eliminate evasion of apoptosis, a ubiquitous cancer hallmark. In these in vitro studies, kinetics and electric field thresholds for several apoptosis characteristics are defined in E4 squamous carcinoma cells (SCC) exposed to ten 300 ns pulses with increasing electric fields. Cell death was >95% at the highest electric field and coincident with phosphatidylserine externalization, caspase and calpain activation in the presence and absence of cytochrome c release, decreases in Bid and mitochondria membrane potential (Δψm) without apparent changes reactive oxygen species levels or in Bcl2 and Bclxl levels. Bid cleavage was caspase-dependent (55–60%) and calcium-depend... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4324701 Thu, 06 Jan 2011 17:55:53 +0100 4324701 Structural analyses of death domains and their interactions http://www.medworm.com/index.php?rid=4317874&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg29567106539l272%2F Abstract  The death domain (DD), which is a versatle protein interaction module, is the prime mediator of the interactions necessary for apoptosis, innate immunity and the necrosis signaling pathway. Because DD mediated signaling events are associated with critical human diseases, studies in these areas are of great biological importance. Accordingly, many biochemical and structural studies of DD have been conducted in the past decade to investigate apoptotic and innate immune signaling. Evaluation of the molecular structure of DD and their interactions with partners have shown the underlying molecular basis for the assembly of DD mediated complexes and for the regulation of apoptosis and innate immunity. This review summarizes the structure and function of various DDs and ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4317874 Tue, 04 Jan 2011 17:54:07 +0100 4317874 Polyclonal rabbit anti-murine plasmacytoma cell globulins induce myeloma cells apoptosis and inhibit tumour growth in mice http://www.medworm.com/index.php?rid=4304717&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4n310v64533115g4%2F In this study, we produced polyclonal rabbit anti-murine plasmacytoma cell immunoglobulin (PAb) by immunizing rabbits with the murine plasmacytoma cell line MPC-11. The isolated PAb bound to plasma surface antigens in several MM cell lines, inhibited their proliferation as revealed by MTT assay, and induce apoptosis as indicated by flow cytometry, microscopic observation of apoptotic changes in morphology, and DNA fragmentation on agarose gels. The cytotoxicity of PAb on MPC-11 cell lines was both dose-dependent and time-dependent; PAb exerted a 50% inhibitory effect on MPC-11 cell viability at a concentration of 200 µg/ml in 48 h. Flow cytometry demonstrated that PAb treatment significantly increased the number of apoptotic cells (48.1%) compared with control IgG (8.3%). ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4304717 Fri, 31 Dec 2010 18:03:34 +0100 4304717 Rapid cold-hardening blocks cold-induced apoptosis by inhibiting the activation of pro-caspases in the flesh fly Sarcophaga crassipalpis http://www.medworm.com/index.php?rid=4304716&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F448548nw28051143%2F Abstract  Apoptosis plays important roles in the selective elimination of sub-lethally damaged cells due to various environmental stresses. The rapid cold-hardening (RCH) response protects insects from the otherwise lethal consequences of injury due to cold-shock. We recently demonstrated that cold shock induces apoptotic cell death in insects and that RCH functions to specifically block cold-shock-induced apoptosis. In the present study we used isolated fat body, midgut, muscle, and Malpighian tubules from adult flesh flies Sarcophaga crassipalpis to test the following hypotheses: (1) cold-induced apoptosis varies among different tissues and (2) RCH blocks the apoptotic pathway by preventing the activation of pro-caspases. Cold-shock induced substantial amounts of apoptotic... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4304716 Fri, 31 Dec 2010 18:03:34 +0100 4304716 Role of Bruton’s tyrosine kinase in macrophage apoptosis http://www.medworm.com/index.php?rid=4302811&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr607045286248p24%2F Abstract  Macrophages and polymorphonuclear cells (PMNs) rapidly respond to microbial and immune inflammatory stimuli and die during these responses. We have shown earlier that many macrophage and PMN functions are compromised in x-linked immunodeficient (Xid) mice with functional deficiency in Bruton’s tyrosine kinase (Btk). We now report that Btk-deficient macrophages show enhanced susceptibility to apoptotic death on exposure to the microbial and immune inflammatory signals bacterial lipopolysaccharide (LPS) and interferon-gamma (IFNγ) in vitro. In vivo in mixed bone marrow (BM) chimeras Btk deficiency leads primarily to loss of peripheral macrophage numbers without affecting BM development, suggesting a role of inflammation-induced apoptosis in regulating macrophage ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4302811 Thu, 30 Dec 2010 18:04:46 +0100 4302811 Panaxydol induces apoptosis through an increased intracellular calcium level, activation of JNK and p38 MAPK and NADPH oxidase-dependent generation of reactive oxygen species http://www.medworm.com/index.php?rid=4301975&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj7384853k17u3350%2F In this study, we demonstrated that panaxydol induced apoptosis preferentially in transformed cells with a minimal effect on non-transformed cells. Furthermore, panaxydol was shown to induce apoptosis through an increase in intracellular Ca2+ concentration ([Ca2+]i), activation of JNK and p38 MAPK, and generation of reactive oxygen species (ROS) initially by NADPH oxidase and then by mitochondria. Panaxydol-induced apoptosis was caspase-dependent and occurred through a mitochondrial pathway. ROS generation by NADPH oxidase was critical for panaxydol-induced apoptosis. Mitochondrial ROS production was also required, however, it appeared to be secondary to the ROS generation by NADPH oxidase. Activation of NADPH oxidase was demonstrated by the membrane translocation of regulatory p47ph... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4301975 Wed, 29 Dec 2010 06:49:01 +0100 4301975 Betanodavirus up-regulates chaperone GRP78 via ER stress: roles of GRP78 in viral replication and host mitochondria-mediated cell death http://www.medworm.com/index.php?rid=4274903&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh47619t01312u581%2F In this study we show that betanodavirus induced ER stress responses up-regulate GRP78, which regulates the viral replication and host cellular mitochondrial-mediated cell death. Betanodavirus (redspotted grouper nervous necrosis virus, RGNNV) infection resulted in the following increased ER stress responses in fish GF-1 grouper fin cells: (1) IRE-1 and ATF-6 sensors at 48 h post-infection (p.i.) that up-regulated chaperone protein GRP78; (2) activation of caspase-12; and (3) PERK phosphorylation and down-regulation of Bcl-2. Analyses of GRP78 functions during viral replication using either loss-of-function or gain-of-function approaches showed that GRP78 over-expression also enhanced viral replication and induced cell death. Then, we found that zfGRP78 localization gradually i... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4274903 Fri, 17 Dec 2010 17:41:06 +0100 4274903 Cell death-resistance of differentiated myotubes is associated with enhanced anti-apoptotic mechanisms compared to myoblasts http://www.medworm.com/index.php?rid=4264329&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu4hn78mw4843p101%2F The objective of this study was to investigate mechanisms underlying apoptosis susceptibility in proliferating myoblasts compared to differentiated myotubes and we hypothesized that cell death-resistance in differentiated myotubes is mediated by enhanced anti-apoptotic pathways. C2C12 myoblasts and myotubes were treated with H2O2 or staurosporine (Stsp) to induce cell death. H2O2 and Stsp induced DNA fragmentation in more than 50% of myoblasts, but in myotubes less than 10% of nuclei showed apoptotic changes. Mitochondrial membrane potential dissipation was detected with H2O2 and Stsp in myoblasts, while this response was greatly diminished in myotubes. Caspase-3 activity was 10-fold higher in myotubes compared to myoblasts, and Stsp caused a significant caspase-3 induction in both. Ho... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4264329 Wed, 15 Dec 2010 15:58:30 +0100 4264329 A shear stress responsive gene product PP1201 protects against Fas-mediated apoptosis by reducing Fas expression on the cell surface http://www.medworm.com/index.php?rid=4207160&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft6017q324u416603%2F Abstract  Cells that form vascular system employ different mechanisms to offset deleterious consequences of exposure to cytokines and cells present in blood. Vascular homeostasis is sustained in part by genes, whose expression increases in response to hemodynamic forces in these cells. PP1201 (also known as RECS1) is one such gene whose expression level increases in response to laminar shear stress. Aged mice deficient in PP1201 are prone to develop cystic medial degeneration (CMD), a form of aortic aneurism manifested with loss of smooth muscle cells and accumulation of basophilic substances. Here we found that higher levels of PP1201 can protect against Fas ligand (FasL)-induced apoptosis. PP1201 interacted with the Fas receptor (CD95/Apo1) and colocalized with it in the Go... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4207160 Wed, 24 Nov 2010 20:20:03 +0100 4207160 The ribonucleotide reductase R1 subunits of herpes simplex virus types 1 and 2 protect cells against TNFα- and FasL-induced apoptosis by interacting with caspase-8 http://www.medworm.com/index.php?rid=4207159&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb760537671524101%2F Abstract  We previously reported that HSV-2 R1, the R1 subunit (ICP10; UL39) of herpes simplex virus type-2 ribonucleotide reductase, protects cells against apoptosis induced by the death receptor (DR) ligands tumor necrosis factor-alpha- (TNFα) and Fas ligand (FasL) by interrupting DR-mediated signaling at, or upstream of, caspase-8 activation. Further investigation of the molecular mechanism underlying HSV-2 R1 protection showed that extracellular-regulated kinase 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3-K)/Akt, NF-κB and JNK survival pathways do not play a major role in this antiapoptotic function. Interaction studies revealed that HSV-2 R1 interacted constitutively with caspase-8. The HSV-2 R1 deletion mutant R1(1-834)-GFP and Epstein–Barr virus (EBV) R1, whi... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4207159 Wed, 24 Nov 2010 20:20:03 +0100 4207159 Defining the core apoptosis pathway in the mosquito disease vector Aedes aegypti: the roles of iap1, ark, dronc, and effector caspases http://www.medworm.com/index.php?rid=4207162&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2644678g36g2151m%2F Abstract  To date, our knowledge of apoptosis regulation in insects comes almost exclusively from the model organism Drosophila melanogaster. In contrast, despite the identification of numerous genes that are presumed to regulate apoptosis in other insects based on sequence homology, little has been done to examine the molecular pathways that regulate apoptosis in other insects, including medically important disease vectors. In D. melanogaster, the core apoptosis pathway consists of the caspase negative regulator DIAP1, IAP antagonists, the initiator caspase Dronc and its activating protein Ark, and the effector caspase DrICE. Here we have studied the functions of several genes from the mosquito disease vector Aedes aegypti that share homology with the core apoptosis genes in... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4207162 Wed, 24 Nov 2010 20:20:02 +0100 4207162 Cellular and biomolecular responses of human ovarian cancer cells to cytostatic dinuclear platinum(II) complexes http://www.medworm.com/index.php?rid=4207161&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Faw16013772p856w3%2F Abstract  Polynuclear platinum(II) complexes represent a class of potential anticancer agents that have shown promising pharmacological properties in preclinical studies. The nature of cellular responses induced by these complexes, however, is poorly understood. In this research, the cellular responses of human ovarian cancer COC1 cells to dinuclear platinum(II) complexes {[cis-Pt(NH3)2Cl]2L1}(NO3)2 (1) and {[cis-Pt(NH3)2Cl]2L2}(NO3)2 (2) (L1 = α,α′-diamino-p-xylene, L2 = 4,4′-methylenedianiline) has been studied using cisplatin as a reference. The effect of platinum complexes on the proliferation, death mode, mitochondrial membrane potential, and cell cycle progression has been examined by MTT assay and flow cytometry. The activation of cell cycle c... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4207161 Wed, 24 Nov 2010 20:20:02 +0100 4207161 Sequential caspase-2 and caspase-8 activation is essential for saikosaponin a-induced apoptosis of human colon carcinoma cell lines http://www.medworm.com/index.php?rid=4202711&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F82161571kq546271%2F In this study, we investigated the signaling pathways implicated in SSa-induced apoptosis of human colon carcinoma (HCC) cell lines. SSa-induced apoptosis of HCC cells was associated with proteolytic activation of caspase-9, caspase-3, and PARP cleavages and decreased levels of IAP family members, such as XIAP and c-IAP-2, but not of survivin. The fluorescence intensity of DiOC6 was significantly reduced after SSa treatment. CsA significantly inhibited SSa-induced loss of mitochondrial transmembrane potential and moderately inhibited SSa-induced cell death. SSa treatment also enhanced the activities of caspase-2 and caspase-8, Bid cleavage, and the conformational activation of Bax. Additionally, SSa-induced apoptosis was inhibited by both the selective caspase-2 inhibitor z-VDVAD-fmk... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4202711 Tue, 23 Nov 2010 18:15:38 +0100 4202711 Dr. Trudy (Helmtrud) Roach (17.09.1944–28.04.2010) http://www.medworm.com/index.php?rid=4202714&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx461622140k85k87%2F Content Type Journal ArticleDOI 10.1007/s10495-010-0563-zAuthors Paul A. Townsend, Faculty of Medicine, University of Southampton, Southampton, UK Journal ApoptosisOnline ISSN 1573-675XPrint ISSN 1360-8185 (Source: Apoptosis) Apoptosis journals http://www.medworm.com/rss/comments.php?id=4202714 Tue, 23 Nov 2010 18:15:36 +0100 4202714 Mutant p53 exhibits trivial effects on mitochondrial functions which can be reactivated by ellipticine in lymphoma cells http://www.medworm.com/index.php?rid=4202713&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F72786q7h74257214%2F In this study, we used doxorubicin, a chemotherapeutic drug, to treat five human lymphoma cell lines with wt, mutant or deficient in p53, to induce p53 activation and mitochondrial translocation. Our results demonstrated that mutant p53, like wt p53, was induced upon doxorubicin treatment. Similarly, a fraction of mutant p53 also translocated to mitochondria. However, Complex I and II activities in the mitochondria were compromised only in wt p53-bearing cells after doxorubicin treatment, but not in mutant p53-bearing cells. Similarly, doxorubicin treatment caused greater cell death only in wt p53-bearing cells, but not in mutant p53-bearing cells. When p53 deficient Ramos cells were transfected with mutant p53 (249S), the cells showed resistance to doxorubicin-induced cell death an... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4202713 Tue, 23 Nov 2010 18:15:36 +0100 4202713 Platinum resistant cancer cells conserve sensitivity to BH3 domains and obatoclax induced mitochondrial apoptosis http://www.medworm.com/index.php?rid=4202712&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp5513510t7415857%2F Abstract  Resistance to cisplatin chemotherapy remains a major hurdle preventing effective treatment of many solid cancers. BAX and BAK are pivotal regulators of the mitochondrial apoptosis pathway, however little is known regarding their regulation in cisplatin resistant cells. Cisplatin induces DNA damage in both sensitive and resistant cells, however the latter exhibits a failure to initiate N-terminal exposure of mitochondrial BAK or mitochondrial SMAC release. Both phenotypes are highly sensitive to mitochondrial permeabilisation induced by exogenous BH3 domain peptides derived from BID, BIM, NOXA (which targets MCL-1 and A1), and there is no significant change in their prosurvival BCL2 protein expression profiles. Obatoclax, a small molecule inhibitor of pro-survival ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4202712 Tue, 23 Nov 2010 18:15:36 +0100 4202712 Ku70 and Rad51 vary in their importance for the repair of doxorubicin- versus etoposide-induced DNA damage http://www.medworm.com/index.php?rid=4202715&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F642632263xm3003p%2F Abstract  For DNA targeting anticancer drugs, cellular DNA repair mechanisms may cause resistance and hamper the therapeutic outcome. DNA damage induced by topoisomerase IIα inhibitors like etoposide and anthracyclines, which are a mainstay of cancer therapy, is also repaired in many cell types, but the impact and precise mechanisms of this repair are still obscure. To investigate the DNA damage response of human adenocarcinoma HT29-cells to doxorubicin and to compare the involvement of Ku70 and Rad51 in the repair of doxorubicin- versus etoposide-induced DNA damage, we assessed cell cycle distribution and cell death, DNA damage, proteins relevant for repair by homologous recombination and non-homologous end-joining, and clonogenicity following exposure to doxorubicin at c... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4202715 Tue, 23 Nov 2010 18:15:35 +0100 4202715 Insulin-like growth factor 1 mediates 5-fluorouracil chemoresistance in esophageal carcinoma cells through increasing survivin stability http://www.medworm.com/index.php?rid=4178655&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm8863x060w8v3047%2F Abstract  Insulin-like growth factor 1 (IGF-1) inhibits 5-fluorouracil (5-Fu)-induced apoptosis in esophageal carcinoma cells; however, the mechanisms for IGF-1-induced 5-Fu chemoresistance remain unknown. In the human esophageal carcinoma cell line, CE48T/VGH, we show that IGF-1 up-regulated survivin expression at the post-transcriptional level and this up-regulation is mediated by both the PI3-K/Akt and casein kinase 2 signaling pathways. We then examine whether IGF-1-induced 5-Fu chemoresistance is mediated through up-regulation of survivin. Ectopic expression of survivin inhibits 5-Fu-induced apoptosis; furthermore, the abolition of survivin expression sensitizes cells to 5-Fu treatment and prevents the anti-apoptotic function of IGF-1 in esophageal carcinoma cell lines.... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4178655 Tue, 16 Nov 2010 19:28:56 +0100 4178655 In vivo imaging of early stage apoptosis by measuring real-time caspase-3/7 activation http://www.medworm.com/index.php?rid=4178656&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft5v2976426q78524%2F Abstract  In vivo imaging of apoptosis in a preclinical setting in anticancer drug development could provide remarkable advantages in terms of translational medicine. So far, several imaging technologies with different probes have been used to achieve this goal. Here we describe a bioluminescence imaging approach that uses a new formulation of Z-DEVD-aminoluciferin, a caspase 3/7 substrate, to monitor in vivo apoptosis in tumor cells engineered to express luciferase. Upon apoptosis induction, Z-DEVD-aminoluciferin is cleaved by caspase 3/7 releasing aminoluciferin that is now free to react with luciferase generating measurable light. Thus, the activation of caspase 3/7 can be measured by quantifying the bioluminescent signal. Using this approach, we have been able to monito... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4178656 Tue, 16 Nov 2010 19:28:49 +0100 4178656 Modulation of ROS/MAPK signaling pathways by okadaic acid leads to cell death via, mitochondrial mediated caspase-dependent mechanism http://www.medworm.com/index.php?rid=4178657&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa2643tp216777145%2F Abstract  Okadaic acid (OA) is a specific and potent protein phosphatase inhibitor and tumor promoter. The present study establishes the role of reactive oxygen species (ROS) and mitogen activated protein kinases in cell death induced by okadaic acid. The study showed that okadaic acid is cytotoxic at 10 nM with an IC50 of 100 nM in U-937 cells. The CVDE assay and mitochondrial dehydrogenase assay showed a time dependent cytotoxicity. The phase contrast visualization of the OA treated cells showed the apoptotic morphology and was confirmed with esterase staining for plasma membrane integrity. OA activated caspases-7, 9 and 3, PARP cleavage and induced nuclear damage in a time and dose dependent manner. Compromised mitochondrial membrane potential, release of cytochrome-c an... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4178657 Tue, 16 Nov 2010 19:28:47 +0100 4178657 Intra-uterine growth restriction is associated with increased apoptosis and altered expression of proteins in the p53 pathway in villous trophoblast http://www.medworm.com/index.php?rid=4142467&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5128g3l1u255l778%2F Abstract  Intrauterine growth restriction (IUGR) affects 3–8% of pregnancies and is associated with altered cell turnover in the villous trophoblast, an essential functional cell type of the human placenta. The intrinsic pathway of apoptosis, particularly p53, is important in regulating placental cell turnover in response to damage. We hypothesised that expression of proteins in the p53 pathway in placental tissue would be altered in IUGR. Expression of constituents of the p53 pathway was assessed using real-time PCR, Western blotting and immunohistochemistry. p53 mRNA and protein expression was increased in IUGR, which localised to the syncytiotrophoblast. Similar changes were noted in p21 and Bax expression. There was no change in the expression of Mdm2, Bak and Bcl-2. ... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4142467 Fri, 05 Nov 2010 11:17:11 +0100 4142467 Granulocyte macrophage-colony stimulating factor shows anti-apoptotic activity in neural progenitor cells via JAK/STAT5-Bcl-2 pathway http://www.medworm.com/index.php?rid=4142468&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl3076074v8853605%2F This study investigated detailed mechanism of GM-CSF involved in its anti-apoptotic activity and regulation of Bcl-2 expression in neural progenitor cells (NPCs) as a model. NPCs were cultured from the brain of E13 ICR mouse. When NPCs were treated with staurosporine at 1 μM, apoptosis occurred in more than 30% of cells in TUNEL assay. However, apoptosis was significantly inhibited by pre-treatment with GM-CSF at 10 ng/ml. Under the same experimental condition, the expression of both Bcl-2 and Bcl-xl was clearly induced by GM-CSF regardless of staurosporine treatment in RT-PCR and Western blot analyses. GM-CSF was shown to induce the expression of Bcl-2 and Bcl-xl via Janus tyrosine kinase (JAK) but not via phosphatidylinositol 3-kinase (PI3K) or RAS-mitogen activated protein k... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4142468 Fri, 05 Nov 2010 11:17:10 +0100 4142468 Synchronized turbo apoptosis induced by cold-shock http://www.medworm.com/index.php?rid=4104813&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk6847493p1703375%2F Abstract  In our research on the role of apoptosis in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE), we aim to evaluate the effects of early and late apoptotic cells and blebs on antigen presenting cells. This requires the in vitro generation of sufficiently large and homogeneous populations of early and late apoptotic cells. Here, we present a quick method encountered by serendipity that results in highly reproducible synchronized homogeneous apoptotic cell populations. In brief, granulocytic 32Dcl3 cells are incubated on ice for 2 h and subsequently rewarmed at 37°C. After 30–90 min at 37°C more than 80–90% of the cells become early apoptotic (Annexin V positive/propidium iodide negative). After 24 h of rewarming at 37... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4104813 Sat, 23 Oct 2010 15:48:02 +0100 4104813 Acetylcholine prevents angiotensin II-induced oxidative stress and apoptosis in H9c2 cells http://www.medworm.com/index.php?rid=4096025&cid=s_35908_67_f&fid=35908&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy83443360771v633%2F In conclusion, ACh prevents Ang II-induced H9c2 cells apoptosis through down-regulation of the AT1 receptor and inhibition of ROS-mediated p38 MAPK activation as well as regulation of Bcl-2, Bax and caspase-3. Content Type Journal ArticleDOI 10.1007/s10495-010-0549-xAuthors Jin-Jun Liu, Department of Pharmacology, Xi’an Jiaotong University, College of Medicine, Xi’an, 710061 People’s Republic of ChinaDong-Ling Li, Department of Pharmacology, Xi’an Jiaotong University, College of Medicine, Xi’an, 710061 People’s Republic of ChinaJuan Zhou, Department of Physiology and pathophysiology, Xi’an Jiaotong University, College of Medicine, Xi’an, 710061 People’s Republic of ChinaLei Sun, Department of Pharmacology, Xi’an Jiaotong University, College of Medicine, Xi’an... Apoptosis journals http://www.medworm.com/rss/comments.php?id=4096025 Wed, 20 Oct 2010 17:59:54 +0100 4096025