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 'Biochemical Pharmacology' source. Wed, 08 Feb 2012 14:04:01 +0100 http://www.medworm.com/index.php?rid=5552101&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22120676%26dopt%3DAbstract Authors: Kim HS, Kim MJ, Kim EJ, Yang Y, Lee MS, Lim JS Abstract Berberine is clinically important natural isoquinoline alkaloid that affects various biological functions, such as cell proliferation, migration and survival. The activation of AMP-activated protein kinase (AMPK) regulates tumor cell migration. However, the specific role of AMPK on the metastatic potential of cancer cells remains largely unknown. The present study investigated whether berberine induces AMPK activation and whether this induction directly affects mouse melanoma cell migration, adhesion and invasion. Berberine strongly increased AMPK phosphorylation via reactive oxygen species (ROS) production. 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), a well-known AMPK activator, also inhibited tumor... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552101 Sat, 31 Dec 2011 01:48:36 +0100 5552101 http://www.medworm.com/index.php?rid=5552098&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22127296%26dopt%3DAbstract Authors: Theodoratos A, Blackburn AC, Cappello J, Tummala P, Dahlstrom JE, Board PG Abstract Dichloroacetic acid (DCA) has potential for use in cancer therapy and the treatment of metabolic acidosis. However, DCA can create a deficiency of glutathione transferase Zeta (GSTZ1-1). Gstz1 knockout mice have elevated oxidative stress and low glutathione levels that increases their sensitivity to acetaminophen toxicity. As it is highly likely that patients that are treated with DCA will develop drug induced GSTZ1-1 deficiency we considered they could be at risk of elevated toxicity if they are exposed to other drugs that cause oxidative stress or consume glutathione (GSH). To test this hypothesis we treated mice with DCA and acetaminophen (APAP). Surprisingly, the mice pre-treated with D... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552098 Sat, 31 Dec 2011 01:48:04 +0100 5552098 http://www.medworm.com/index.php?rid=5552097&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138288%26dopt%3DAbstract Authors: Tang CH, Tsai CC Abstract Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family that is associated with the disease status and outcomes of cancers. However, the effect of CCL2 on migration activity in human chondrosarcoma cells is mostly unknown. Here we found that CCL2 increased the migration and expression of matrix metalloproteinase (MMP)-9 in human chondrosarcoma cells. CCL2-mediated migration and MMP-9 up-regulation were attenuated by CCR2, Ras, Raf-1, and MEK inhibitor. Activation of the Ras, Raf-1, MEK, ERK, and NF-κ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552097 Sat, 31 Dec 2011 01:47:53 +0100 5552097 http://www.medworm.com/index.php?rid=5552095&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138446%26dopt%3DAbstract Authors: McNamara AV, Barclay M, Watson AJ, Jenkins JR Abstract Hsp90 and topoisomerase I are both targets for chemotherapeutic agents. Topoisomerase I poisons are standard clinical treatments, whilst Hsp90 inhibitors are progressing through clinical trials. We have demonstrated that when an Hsp90 inhibitor and topoisomerase I poison are combined they produce a synergistic increase in apoptosis in both p53(+/+) and p53(-/-) HCT116 human colon cancer cells. Lack of p53 is associated with an increase in sensitivity to the combination treatment; p53(+/+) cells treated with the topoisomerase I poison topotecan (TPT) arrest at G2, whereas in p53(-/-) cells the additional presence of the Hsp90 inhibitor geldanamycin (GA) selectively abrogates the G2M checkpoint. More importantly we repor... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552095 Sat, 31 Dec 2011 01:47:33 +0100 5552095 http://www.medworm.com/index.php?rid=5552094&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138447%26dopt%3DAbstract Authors: Loo TW, Bartlett MC, Shi L, Clarke DM Abstract The most common cause of cystic fibrosis is deletion of Phe508 in the first nucleotide-binding domain (NBD) of the CFTR chloride channel, which inhibits protein folding. ΔF508 CFTR can be rescued by indirect approaches such as low temperature but the protein is unstable. Here, we tested our predictions that (1) other CFTR mutants such V232D and H1085R were more stable at the cell surface than ΔF508 CFTR after low temperature rescue and (2) the advantages of rescue with specific correctors (pharmacological chaperones) are that they may stabilize ΔF508 CFTR and increase the effectiveness of the correctors by bypassing drug pumps such as P-glycoprotein (P-gp) (increased bioavailability). It was found that the stability of muta... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552094 Sat, 31 Dec 2011 01:47:24 +0100 5552094 http://www.medworm.com/index.php?rid=5552090&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22146584%26dopt%3DAbstract This study evaluated the mode of action, antimicrobial activities, and mammalian cell cytotoxicity of the thiadiazolidinone family in order to assess its potential for development as a therapeutic agent against MRSA. The thiadiazolidones inhibited Alr activity with 50% inhibitory concentrations (IC(50)) ranging from 0.36 to 6.4μM, and they appear to inhibit the enzyme irreversibly. The series inhibited the growth of S. aureus, including MRSA strains, with minimal inhibitory concentrations (MICs) ranging from 6.25 to 100μg/ml. The antimicrobial activity showed selectivity against Gram-positive bacteria and fungi, but not Gram-negative bacteria. The series inhibited human HeLa cell proliferation. Lead development centering on the thiadiazolidinone series would require additional medicinal ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552090 Sat, 31 Dec 2011 01:46:41 +0100 5552090 http://www.medworm.com/index.php?rid=5552088&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22153861%26dopt%3DAbstract In this report, two novel structurally related compounds, A-686085 and A-1048400, were identified that potently block N-type (IC(50)=0.8μM and 1.4μM, respectively) and T-type (IC(50)=4.6μM and 1.2μM, respectively) Ca(2+) channels in FLIPR based Ca(2+) flux assays. A-686085 also potently blocked L-type Ca(2+) channels (EC(50)=0.6μM), however, A-1048400 was much less active in blocking this channel (EC(50)=28μM). Both compounds dose-dependently reversed tactile allodynia in a model of capsaicin-induced secondary hypersensitivity with similar potencies (EC(50)=300-365ng/ml). However, A-686085 produced dose-related decreases in mean arterial pressure at antinociceptive plasma concentrations in the rat, while A-1048400 did not significantly alter hemodynamic function at supra-efficacious ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552088 Sat, 31 Dec 2011 01:46:20 +0100 5552088 http://www.medworm.com/index.php?rid=5552086&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155307%26dopt%3DAbstract In this study, we investigated the effects of HO-1 induction on OA osteoblast metabolism. HO-1 was induced with cobalt protoporphyrin IX (CoPP) and by transduction with LV-HO-1. In osteoblasts stimulated with interleukin (IL)-1β, CoPP enhanced mineralization, the expression of a number of markers of osteoblast differentiation such as Runx2, bone morphogenetic protein-2, osteocalcin, and collagen 1A1 and 1A2, as well as the ratio osteoprotegerin/receptor activator of nuclear factor-κB ligand. HO-1 induction significantly reduced the expression of matrix metalloproteinase (MMP)-1, MMP-2 and MMP-3, and the production of pro-inflammatory cytokines such as tumor necrosis factor-α and IL-6 whereas IL-10 levels increased. HO-1 also exerted inhibitory effects on prostaglandin (PG)E(2) productio... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552086 Sat, 31 Dec 2011 01:45:59 +0100 5552086 http://www.medworm.com/index.php?rid=5552062&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22202439%26dopt%3DAbstract Authors: Verron E, Loubat A, Carle GF, Vignes-Colombeix C, Strazic I, Guicheux J, Rochet N, Bouler JM, Scimeca JC Abstract We had previously reported that gallium (Ga) inhibited both the differentiation and resorbing activity of osteoclasts in a dose-dependent manner. To provide new insights into Ga impact on osteoclastogenesis, we investigated here the molecular mechanisms of Ga action on osteoclastic differentiation of monocytes upon Rankl treatment. We first observed that Ga treatment inhibited the expression of Rankl-induced early differentiation marker genes, while the same treatment performed subsequently did not modify the expression of late differentiation marker genes. Focusing on the early stages of osteoclast differentiation, we observed that Ga considerably disturbed bo... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552062 Mon, 19 Dec 2011 05:00:00 +0100 5552062 http://www.medworm.com/index.php?rid=5552070&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192818%26dopt%3DAbstract Authors: Fleck MW, Thomson JL, Hough LB Abstract There is ample pharmacological and physiological evidence for yet unidentified histamine receptors in mammalian brain that are linked to a Cl(-) conductance. In invertebrates, two histamine-gated chloride channels (HisCl α1 and α2) are already well known. HisCl channels are members of the Cys-loop receptor superfamily of ligand-gated ion channels and are closely related to the mammalian GABA(A) and glycine receptors (GlyR). Indeed, they share particularly strong homology within the ligand binding and ion channel domains. Here we discuss the possibility that mammalian HisCl channels might exist among the known GABA(A) or GlyR subunits. Studies published to date support this hypothesis, including evidence for direct histamine gating ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552070 Fri, 16 Dec 2011 05:00:00 +0100 5552070 http://www.medworm.com/index.php?rid=5552069&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192819%26dopt%3DAbstract Authors: Lee AJ, Swanton C Abstract Intrinsic and acquired drug resistance leads to the eventual failure of cancer treatment regimens in the majority of advanced solid tumours. Understanding drug resistance mechanisms will prove vital in the future development of personalised therapeutic approaches. Functional genomics technologies may permit the discovery of predictive biomarkers by unravelling pathways involved in drug resistance and allow the systematic identification of novel therapeutic targets. Such technologies offer the opportunity to develop personalised treatments and diagnostic tools that may improve the survival and quality of life of patients with cancer. However, despite progress in biomarker and drug target discovery, inter-tumour and intra-tumour molecular heterogen... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552069 Fri, 16 Dec 2011 05:00:00 +0100 5552069 http://www.medworm.com/index.php?rid=5552067&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192821%26dopt%3DAbstract Authors: Breyer J, Samarin J, Rehm M, Lautscham L, Fabry B, Goppelt-Struebe M Abstract Rho kinases are major regulators of actin cytoskeletal organization and cell motility. Depending on the model system, inhibitors of Rho kinases (ROCK) have been reported to increase or decrease endothelial cell migration. In the present study we investigated the effect of Rho kinase inhibitors on microvascular endothelial cell migration with a special focus on the isoform ROCK2. Migration of microvascular endothelial cells was analyzed in a wound-healing, a spheroid-on-collagen migration assay and in cells embedded in collagen-1 gels. The non-selective Rho kinase inhibitor H1152 was compared to the selective ROCK2 inhibitor SLX2119 and to siRNA knock down. Non-selective inhibition of Rho kinases ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552067 Fri, 16 Dec 2011 05:00:00 +0100 5552067 http://www.medworm.com/index.php?rid=5552066&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22197587%26dopt%3DAbstract Authors: Noh M Abstract Lineage commitment of human bone marrow mesenchymal stem cells (hBM-MSCs) to adipocytes or osteoblasts has been suggested as a model system to study the relationship between type II diabetes and abnormal bone metabolism. Leptin and IL-17A inhibit adipogenesis whereas they promote osteogenesis in MSCs. Due to pathophysiologic roles of IL-17A in human metabolic diseases and bone metabolism, it was evaluated whether IL-17A-dependent inverse regulation on adipogenesis and osteogenesis was related to endogenous leptin production in hBM-MSCs. In the analysis of adiponectin and leptin secretion profiles of hBM-MSCs in response to various combinations of differentiation inducing factors, it was found that dexamethasone, a common molecule used for both adipogenesis a... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552066 Fri, 16 Dec 2011 05:00:00 +0100 5552066 http://www.medworm.com/index.php?rid=5552065&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22197588%26dopt%3DAbstract Authors: Chatenet D, Nguyen QT, Létourneau M, Dupuis J, Fournier A Abstract In recent years, several studies have demonstrated that urotensin II (UII) and urotensin II-related peptide (URP) can exhibit differential biological activity. So far, known antagonists of the urotensin II receptor (UT) are of limited usefulness for investigating the specific pathophysiological role of UII or URP. Therefore, identification of new compounds able to discriminate UII- and URP-associated biological activities is crucially needed. In the present study, we report preliminary data regarding the pharmacological properties of a novel UT ligand termed urocontrin, i.e. [Bip(4)]URP, that is able to reduce the ex vivo efficacy of hUII- but not URP-induced vasoconstriction in rat aortic rings. In vivo s... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552065 Fri, 16 Dec 2011 05:00:00 +0100 5552065 http://www.medworm.com/index.php?rid=5552064&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22197899%26dopt%3DAbstract Authors: Guyot E, Coumoul X, Chassé JF, Khallouki F, Savouret JF, Poirot M, Barouki R Abstract Paraoxonase 1 (PON1) is a high-density lipoprotein-associated enzyme, synthesized in the liver and secreted into the blood. PON1 displays antioxidant properties and is involved in organophosphorous compounds and oxidized lipids degradation. Because of these beneficial effects, pharmacological regulation of PON1 appears to be highly relevant in toxicology and cardiology. Recent studies undertaken on the regulation of the PON1 promoter in our laboratory have identified resveratrol, through its activation of the Aryl hydrocarbon Receptor (AhR), as a putative inducer of PON1. We have tested a new modulator of AhR, (Z)-2,3-bis (4-nitrophenyl)-acrylonitrile, and established that it is a more p... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552064 Fri, 16 Dec 2011 05:00:00 +0100 5552064 http://www.medworm.com/index.php?rid=5552063&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198485%26dopt%3DAbstract CONCLUSIONS: PARP1 is a regulator of basal cellular energetics in resting endothelial and epithelial cells. Furthermore, endothelial cells respond with a decrease in their mitochondrial reserve capacity during low-level oxidative stress, an effect, which is attenuated by PARP1 inhibition. While PARP1 is a regulator of oxidative phosphorylation in resting and oxidatively stressed cells, it only exerts a minor effect on glycolysis. PMID: 22198485 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552063 Fri, 16 Dec 2011 05:00:00 +0100 5552063 http://www.medworm.com/index.php?rid=5552068&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192820%26dopt%3DAbstract In conclusion, tight coupling of Ah receptor- and Nrf2-regulated enzymes may prevent quinone-mediated oxidative and ER stress. PMID: 22192820 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552068 Wed, 14 Dec 2011 05:00:00 +0100 5552068 http://www.medworm.com/index.php?rid=5552071&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22182429%26dopt%3DAbstract This study supports the hypothesis that both oxic and hypoxic cell killing by CEN-209 is mechanistically analogous to tirapazamine and is dependent on oxidative DNA damage repaired via multiple pathways. However, HAPs that generate DNA interstrand cross-links, such as TH-302 and PR-104, may be more suitable than benzotriazine di-N-oxides for exploiting reported HR repair defects in hypoxic tumour cells. PMID: 22182429 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552071 Tue, 13 Dec 2011 05:00:00 +0100 5552071 http://www.medworm.com/index.php?rid=5552081&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172989%26dopt%3DAbstract Authors: Duez H, Cariou B, Staels B Abstract Although being a primary objective in the management of type 2 diabetes, optimal glycaemic control is difficult to achieve and usually not maintained over time. Type 2 diabetes is a complex pathology, comprising altered insulin sensitivity and impaired insulin secretion. Recent advances in the understanding of the physiological functions of incretins and their degrading enzyme dipeptidyl-peptidase (DPP)-4 have led to the 'discovery' of a new class of oral anti-diabetic drugs. Several DPP-4 inhibitors (or gliptins) with different chemical structures are now available. These agents inhibit the degradation of the incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and hence potentiate glucose-dep... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552081 Mon, 12 Dec 2011 05:00:00 +0100 5552081 http://www.medworm.com/index.php?rid=5552078&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177985%26dopt%3DAbstract Authors: Kalderén C, Forsgren M, Karlström U, Stefansson K, Svensson R, Berglund MM, Palm G, Selander M, Sundbom M, Nilsson J, Sjögren A, Zachrisson K, Gelius SS Abstract The truncated [1+9-76] CCL2 analogue, also known as 7ND, has been described in numerous reports as an anti-inflammatory and anti-fibrotic agent in a wide spectrum of animal models, e.g. models of cardiovascular disease, graft versus host disease and bleomycin-induced pulmonary fibrosis. 7ND has been reported to function as a competitive inhibitor of CCL2 signaling via CCR2 in human in vitro systems. In contrast, the mechanistic basis of 7ND action in animal models has not been previously reported. Here we have studied how 7ND interacts with CCL2 and CCR2 of murine origin. Surprisingly, 7ND was shown to be a wea... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552078 Fri, 09 Dec 2011 05:00:00 +0100 5552078 http://www.medworm.com/index.php?rid=5552077&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177986%26dopt%3DAbstract Authors: Erkhembayar S, Mollbrink A, Eriksson LC Abstract Selenium in supra-nutritional doses is tumour-preventative in animal models and in humans. In this work, we have compared the effect of sodium selenite on tumour growth in a rat hepatocarcinogenesis model with the effect of sodium selenite on the regeneration of liver mass after partial hepatectomy. In the tumour model, 5μg/mL sodium selenite in the drinking water reduced the rate of tumour growth for up to 12 months after initiation; the volume fraction of liver cancers was 14±4% with a mean bromodeoxyuridine-index of 19±11% in the treated rats compared to a volume fraction of 26±7% with a mean bromodeoxyuridine-index of 42±27% in the control rats. Despite its efficacy in reducing tumour growth, 5μg/mL sodium selenite... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552077 Fri, 09 Dec 2011 05:00:00 +0100 5552077 http://www.medworm.com/index.php?rid=5552076&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177987%26dopt%3DAbstract Authors: Lavaud A, Soleti R, Hay AE, Richomme P, Guilet D, Andriantsitohaina R Abstract Clusiaceae plants display high contents of xanthones and coumarins, the effects of which on endothelium, more particularly on angiogenesis, have not been assessed yet. We screened the capacity of six molecules from Clusiaceae - belonging to xanthones, coumarins and acid chromanes classes - to induce endothelial-dependent relaxation on mice aortic rings. Endothelial nitric oxide (NO) production was assessed in endothelial cell line using electron paramagnetic resonance technique. Then, the capacity of these molecules to induce capillary-like structures of endothelial cells was assessed. Cellular processes implicated in angiogenesis (adhesion, migration and proliferation) and Western blot analyses... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552076 Fri, 09 Dec 2011 05:00:00 +0100 5552076 http://www.medworm.com/index.php?rid=5552072&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178720%26dopt%3DAbstract This study provides the first evidence that E804, a novel indirubin derivative, could more effectively inhibit angiogenesis. With the improved anti-angiogenic potency when compared with indirubin-3'oxime, E804 would be a new potential candidate in the treatment of angiogenesis-dependent diseases. PMID: 22178720 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552072 Fri, 09 Dec 2011 05:00:00 +0100 5552072 http://www.medworm.com/index.php?rid=5552080&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172990%26dopt%3DAbstract Authors: Kovac S, Loh SW, Lachal S, Shulkes A, Baldwin GS Abstract The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated gastrins in vitro and in vivo. Bi(3+) ions also bind to glycine-extended gastrin17 (Ggly), but inhibit Ggly-induced cell proliferation and migration in gastrointestinal cell lines in vitro. The aims of the present study were firstly, to establish the mechanism by which Bi(3+) ions inhibit the binding of Fe(3+) ions to Ggly, and secondly, to test the effect of Bi(3+) ions on the activity of non-amidated gastrins in vivo. The interaction between Bi(3+) ions, Fe(3+) ions and Ggly was investigated by ultraviolet spectroscopy. The effect of Bi(3+) ions on colorectal mucosal proli... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552080 Thu, 08 Dec 2011 05:00:00 +0100 5552080 http://www.medworm.com/index.php?rid=5552079&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177984%26dopt%3DAbstract Authors: Catucci G, Gilardi G, Jeuken L, Sadeghi SJ Abstract Human flavin-containing monooxygenase 3 (hFMO3) is a microsomal drug-metabolizing monooxygenase that catalyzes the NADPH-dependent oxygenation of a wide range of drugs and xenobiotics which contain a soft-nucleophiles, usually sulfur or nitrogen. As the release from the microsomal membranes can facilitate the in vitro experimental determination of drug metabolism by hFMO3, in this work we identified and eliminated the membrane anchoring sequence without affecting the activity of the enzyme and producing a soluble active enzyme. The truncated hFMO3 carrying a C-terminal deletion of 17 amino acids (tr-hFMO3) was expressed and purified from the cytosolic fraction. The tr-hFMO3 proves to be detached from the membrane, properl... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552079 Thu, 08 Dec 2011 05:00:00 +0100 5552079 http://www.medworm.com/index.php?rid=5552073&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178719%26dopt%3DAbstract Authors: Bucolo C, Leggio GM, Maltese A, Castorina A, D'Agata V, Drago F Abstract The aim of the present study was to investigate the role of D(3) receptor on intraocular pressure regulation using WT and KO D(3)R(-/-) mice. Both mice were used with normal eye pressure or steroid-induced ocular hypertension. As measured by tonometry, the topical application of 7-OH-DPAT, a dopamine D(3)-preferring receptor agonist, significantly decreased, in a dose-dependent manner, the intraocular pressure in WT mice both in an ocular normotensive group and an ocular hypertensive group. Pretreatment with U-99194A, a D(3) receptor antagonist, reverted 7-OH-DPAT induced ocular hypotension in WT mice. No change of intraocular pressure was observed after topical application of 7-OH-DPAT in KO D(3)R(-/... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552073 Thu, 08 Dec 2011 05:00:00 +0100 5552073 http://www.medworm.com/index.php?rid=5552082&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155350%26dopt%3DAbstract Authors: Espona-Fiedler M, Soto-Cerrato V, Hosseini A, Lizcano JM, Guallar V, Quesada R, Gao T, Pérez-Tomás R Abstract The PI3K/AKT/mTOR signaling pathway regulates cell proliferation, survival and angiogenesis. The mammalian target of rapamycin (mTOR) is a protein kinase ubiquitously expressed within cells that regulates cell growth and survival by integrating nutrient and hormonal signals. mTOR exists in two complexes, mTORC1 and mTORC2. Hyperactivation of the mTOR protein has been linked to development of cancer, raising mTOR as an attractive target for cancer therapy. Prodigiosin (PG) and obatoclax (OBX), two members of the prodiginines family, are small molecules with anticancer properties which are currently under clinical trials. In the present paper, we demonstrate that m... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552082 Tue, 06 Dec 2011 05:00:00 +0100 5552082 http://www.medworm.com/index.php?rid=5552085&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155308%26dopt%3DAbstract Authors: Papp-Wallace KM, Bethel CR, Gootz TD, Shang W, Stroh J, Lau W, McLeod D, Price L, Marfat A, Distler A, Drawz SM, Chen H, Harry E, Nottingham M, Carey PR, Buynak JD, Bonomo RA Abstract β-Lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) contribute significantly to the longevity of the β-lactam antibiotics used to treat serious infections. In the quest to design more potent compounds and to understand the mechanism of action of known inhibitors, 6β-(hydroxymethyl)penicillanic acid sulfone (6β-HM-sulfone) was tested against isolates expressing the class A TEM-1 β-lactamase and a clinically important variant of the AmpC cephalosporinase of Pseudomonas aeruginosa, PDC-3. The addition of the 6β-HM-sulfone inhibitor to ampicillin was highly effective. 6β-HM... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552085 Fri, 02 Dec 2011 05:00:00 +0100 5552085 http://www.medworm.com/index.php?rid=5552084&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155309%26dopt%3DAbstract Authors: Schulz S, Ninke S, Watzer B, Nüsing RM Abstract Under certain pathological conditions, e.g., infectious or neoplastic diseases, application of ozone exerts therapeutic effects. However, pharmacological mechanisms are not understood. Since an interaction with the arachidonic acid metabolism is suggested we investigated the effect of intraperitoneal insufflation of ozone on prostanoid system in vivo. Upon ozone application (4mg/kg) to rats we observed an approximate 3-fold increase in excretion rate of 6-keto-prostaglandin (PG) F(1α) and of 2,3-dinor-6-keto-PGF(1α), the measurable stable products of prostacyclin. In plasma and vessel tissue 6-keto-PGF(1α) concentration was also significantly increased. In contrast, excretion rates for PGE(2) and thromboxane (TX) B(2) did... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552084 Fri, 02 Dec 2011 05:00:00 +0100 5552084 http://www.medworm.com/index.php?rid=5552083&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155310%26dopt%3DAbstract Authors: Dutra RC, de Cezaro de Souza PR, Bento AF, Marcon R, Bicca MA, Pianowski LF, Calixto JB Abstract Multiple sclerosis (MS) is a severe chronic T cell-mediated autoimmune inflammatory disease of the central nervous system (CNS), the existing therapy of which is only partially effective and is associated with undesirable side effects. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological properties and is considered to have anti-inflammatory action. However there are no reports about the effects and mechanisms of euphol in experimental autoimmune encephalomyelitis (EAE), an established model of MS. Here we report the effects and the underlying mechanisms of action of euphol in EAE. Euphol (1-10mg/kg) was administered orally at different time-points of ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552083 Thu, 01 Dec 2011 05:00:00 +0100 5552083 http://www.medworm.com/index.php?rid=5552087&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22155295%26dopt%3DAbstract Authors: Tew KD PMID: 22155295 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552087 Tue, 29 Nov 2011 05:00:00 +0100 5552087 http://www.medworm.com/index.php?rid=5552096&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138445%26dopt%3DAbstract Authors: Backos DS, Franklin CC, Reigan P Abstract Chemotherapy is central to the current treatment modality for primary human brain tumors, but despite high-dose and intensive treatment regimens there has been little improvement in patient outcome. The development of tumor chemoresistance has been proposed as a major contributor to this lack of response. While there have been some improvements in our understanding of the molecular mechanisms underlying brain tumor drug resistance over the past decade, the contribution of glutathione (GSH) and the GSH-related enzymes to drug resistance in brain tumors have been largely overlooked. GSH constitutes a major antioxidant defense system in the brain and together with the GSH-related enzymes plays an important role in protecting cells aga... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552096 Mon, 28 Nov 2011 05:00:00 +0100 5552096 http://www.medworm.com/index.php?rid=5552093&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22142888%26dopt%3DAbstract Authors: Loehberg CR, Strissel PL, Dittrich R, Strick R, Dittmer J, Dittmer A, Fabry B, Kalender WA, Koch T, Wachter DL, Groh N, Polier A, Brandt I, Lotz L, Hoffmann I, Koppitz F, Oeser S, Mueller A, Fasching PA, Lux MP, Beckmann MW, Schrauder MG Abstract PI3K/Akt/mTOR and p53 signaling pathways are frequently deregulated in tumors. The anticancer drug RAD001 (everolimus) is a known mTOR-inhibitor, but mTOR-inhibition leads to phosphorylation of Akt inducing resistance against RAD001 treatment. There is growing evidence that conflicting signals transduced by the oncogene Akt and the tumorsuppressor p53 are integrated via negative feedback between the two pathways. We previously showed that the anti-malarial Chloroquine, a 4-alkylamino substituted quinoline, is a p53 activator and r... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552093 Mon, 28 Nov 2011 05:00:00 +0100 5552093 http://www.medworm.com/index.php?rid=5552092&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22146582%26dopt%3DAbstract We examined the action of carvedilol on cloned Kv1.5 expressed in CHO cells, using the whole-cell patch clamp technique. Carvedilol reduced the peak amplitude of Kv1.5 and accelerated the inactivation rate in a concentration-dependent manner with an IC(50) of 2.56μM. Using a first-order kinetics analysis, we calculated k(+1)=19.68μM(-1)s(-1) for the association rate constant, and k(-1)=44.89s(-1) for the dissociation rate constant. The apparent K(D) (k(-1)/k(+1)) was 2.28μM, which is similar to the IC(50) value. Other β-adrenergic blockers (alprenolol, oxprenolol and carteolol) had little or no effect on Kv1.5 currents. Carvedilol slowed the deactivation time course, resulting in a tail crossover phenomenon. Carvedilol-induced block was voltage-dependent in the voltage range for channe... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552092 Mon, 28 Nov 2011 05:00:00 +0100 5552092 http://www.medworm.com/index.php?rid=5552091&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22146583%26dopt%3DAbstract Authors: Mosi RM, Anastassova V, Cox J, Darkes MC, Idzan SR, Labrecque J, Lau G, Nelson KL, Patel K, Santucci Z, Wong RS, Skerlj RT, Bridger GJ, Huskens D, Schols D, Fricker SP Abstract In order to enter and infect human cells HIV must bind to CD4 in addition to either the CXCR4 or the CCR5 chemokine receptor. AMD11070 was the first orally available small molecule antagonist of CXCR4 to enter the clinic. Herein we report the molecular pharmacology of AMD11070 which is a potent inhibitor of X4 HIV-1 replication and the gp120/CXCR4 interaction. Using the CCRF-CEM T cell line that endogenously expresses CXCR4 we have demonstrated that AMD11070 is an antagonist of SDF-1α ligand binding (IC(50)=12.5±1.3nM), inhibits SDF-1 mediated calcium flux (IC(50)=9.0±2.0nM) and SDF-1α mediated ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552091 Mon, 28 Nov 2011 05:00:00 +0100 5552091 http://www.medworm.com/index.php?rid=5552089&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22146585%26dopt%3DAbstract Authors: Lakshmanan AP, Meilei H, Sukumaran V, Soetikno V, Suzuki K, Kodama M, Nagata M, Takagi R, Watanabe K Abstract There are evidences that the activation of AMPK is playing pivotal role in the lipid and glucose metabolism. It has been reported that both the AMPK and angiotensin-II acts as a negative regulator for each protein. It has been well proven that the MAPK cascade could be modulated by the presence of angiotensin-II. Moreover, studies were shown that p38 MAPK stimulates glucose uptake through the AMPK activation. Therefore, we speculate and tried to demonstrate that the modulation of AT-R/MAPK pathway through AMPK might play crucial roles for the pathogenesis of diabetic cardiomyopathy, using the transgenic (Spontaneous Diabetic Torii - SDT) rats. We performed Western ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552089 Mon, 28 Nov 2011 05:00:00 +0100 5552089 http://www.medworm.com/index.php?rid=5552100&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22120677%26dopt%3DAbstract Authors: Perego P, Zuco V, Gatti L, Zunino F Abstract Epigenetic mechanisms may contribute to drug resistance by interfering with tumor growth regulatory pathways and pro-apoptotic programs. Since gene expression is regulated by acetylation status of histones, a large variety of histone deacetylase (HDAC) inhibitors have been studied as antitumor agents. On the basis of their pro-apoptotic activity, HDAC inhibitors have been combined with conventional antitumor agents or novel target-specific agents to increase susceptibility to apoptosis and drug sensitivity of cancer cells. Several combination strategies including HDAC inhibitors have been explored in preclinical studies. Promising therapeutic effects have been reported in combination with DNA damaging agents, taxanes, targeted a... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552100 Tue, 22 Nov 2011 05:00:00 +0100 5552100 http://www.medworm.com/index.php?rid=5552099&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22120678%26dopt%3DAbstract Authors: Lu X, Xiao L, Wang L, Ruden DM Abstract Hsp90 is a chaperone protein that interacts with client proteins that are known to be in the cell cycle, signaling and chromatin-remodeling pathways. Hsp90 inhibitors act additively or synergistically with many other drugs in the treatment of both solid tumors and leukemias in murine tumor models and humans. Hsp90 inhibitors potentiate the actions of anti-cancer drugs that target Hsp90 client proteins, including trastuzumab (Herceptin™) which targets Her2/Erb2B, as Hsp90 inhibition elicits the drug effects in cancer cell lines that are otherwise resistant to the drug. A phase II study of the Hsp90 inhibitor 17-AAG and trastuzumab showed that this combination therapy has anticancer activity in patients with HER2-positive metastatic ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552099 Tue, 22 Nov 2011 05:00:00 +0100 5552099 http://www.medworm.com/index.php?rid=5552102&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22119240%26dopt%3DAbstract Authors: Scott Bitner R Abstract CREB-mediated transcription can be initiated by membrane receptor stimulation and subsequent activation of intracellular pathways to the cell nucleus, and has been described as a molecular switch required for learning and memory. While CREB dimers are thought to be constitutively bound to response elements on DNA under basal conditions, it is CREB phosphorylation that is believed to be responsible for transcriptional activation leading to gene products such as BDNF that play a key role in synaptic plasticity and cognitive function. Conversely, preclinical and clinical findings now suggest that impaired CREB phosphorylation may be a pathological component in neurodegenerative disorders, in particular Alzheimer's disease (AD). In this regard, pharmaco... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5552102 Sat, 19 Nov 2011 05:00:00 +0100 5552102 http://www.medworm.com/index.php?rid=5444092&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22108225%26dopt%3DAbstract In this study, the expression and roles of volume-activated chloride channels in cell growth were investigated in the poorly-differentiated human nasopharyngeal carcinoma cell (CNE-2Z) and its counterpart, the normal human nasopharyngeal epithelial cell (NP69-SV40T). Consistent with growth ability, the background chloride currents recorded under isotonic condition, the volume-activated chloride currents induced by 47% hypotonic challenges and the hyponinicity-induced regulatory volume decrease (RVD) were much larger in CNE-2Z cells than in NP69-SV40T cells, suggesting the up-regulation of expression of volume-activated chloride channels in cancerous cells. This was proved by the up-regulation of ClC-3 proteins, a candidate of volume-activated chloride channels, in the cancerous cells. Func... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5444092 Fri, 18 Nov 2011 05:00:00 +0100 5444092 http://www.medworm.com/index.php?rid=5444093&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22108175%26dopt%3DAbstract Authors: Franco A, Kompella SN, Akondi K, Melaun C, Daly NL, Luetje CW, Alewood PF, Craik DJ, Adams DJ, Marí F Abstract Neuronal nicotinic acetylcholine receptors (nAChRs) play pivotal roles in the central and peripheral nervous systems. They are implicated in disease states such as Parkinson's disease and schizophrenia, as well as addictive processes for nicotine and other drugs of abuse. Modulation of specific nAChRs is essential to understand their role in the CNS. α-Conotoxins, disulfide-constrained peptides isolated from the venom of cone snails, potently inhibit nAChRs. Their selectivity varies markedly depending upon the specific nAChR subtype/α-conotoxin pair under consideration. Thus, α-conotoxins are excellent probes to evaluate the functional roles of nAChRs subtypes... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5444093 Wed, 16 Nov 2011 05:00:00 +0100 5444093 http://www.medworm.com/index.php?rid=5444096&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100984%26dopt%3DAbstract Authors: Xie L, Kassner M, Munoz RM, Que Q, Kiefer J, Zhao Y, Mousses S, Yin H, Von Hoff DD, Han H Abstract Aurora kinases are a family of mitotic kinases that play important roles in the tumorigenesis of a variety of cancers including pancreatic cancer. A number of Aurora kinase inhibitors (AKIs) are currently being tested in preclinical and clinical settings as anti-cancer therapies. However, the antitumor activity of AKIs in clinical trials has been modest. In order to improve the antitumor activity of AKIs in pancreatic cancer, we utilized a kinome focused RNAi screen to identify genes that, when silenced, would sensitize pancreatic cancer cells to AKI treatment. A total of 17 kinase genes were identified and confirmed as positive hits. One of the hits was the platelet-derived ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5444096 Tue, 15 Nov 2011 05:00:00 +0100 5444096 http://www.medworm.com/index.php?rid=5444095&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100985%26dopt%3DAbstract Authors: Alam SR, Newby DE, Henriksen PA Abstract Neutrophils and neutrophil-derived elastases play a major role in the regulation of vascular injury and inflammation, such as ischemia-reperfusion injury. Elafin is an endogenous inhibitor of neutrophil-derived elastases with numerous anti-inflammatory functions that include modulation of inflammatory cytokine release as well as innate and adaptive immunity. It is produced by epithelial tissues including the skin and respiratory system that have adapted to respond to the microbial and chemical insults that lead to inflammation. The production of peptides like elafin with multi-faceted anti-inflammatory activity is an important part of this adaptation. Although not directly expressed within the cardiovascular system itself, pre-clini... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5444095 Tue, 15 Nov 2011 05:00:00 +0100 5444095 http://www.medworm.com/index.php?rid=5444094&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100986%26dopt%3DAbstract Authors: Pravetoni M, Keyler DE, Pidaparthi RR, Carroll FI, Runyon SP, Murtaugh MP, Earley CA, Pentel PR Abstract Nicotine conjugate vaccine efficacy is limited by the concentration of nicotine-specific antibodies that can be reliably generated in serum. Previous studies suggest that the concurrent use of 2 structurally distinct nicotine immunogens in rats can generate additive antibody responses by stimulating distinct B cell populations. In the current study we investigated whether it is possible to identify a third immunologically distinct nicotine immunogen. The new 1'-SNic immunogen (2S)-N,N'-(disulfanediyldiethane-2,1-diyl)bis[4-(2-pyridin-3-ylpyrrolidin-1-yl)butanamide] conjugated to keyhole limpet hemocyanin (KLH) differed from the existing immunogens 3'-AmNic-rEPA and 6-CM... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5444094 Tue, 15 Nov 2011 05:00:00 +0100 5444094 http://www.medworm.com/index.php?rid=5444098&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100726%26dopt%3DAbstract In this study, we investigated whether S. chinensis extract and its active ingredients inhibit TGFβ1 signaling in A7r5 vascular smooth muscle cells. We found that S. chinensis extract suppressed TGFβ1 signaling via inhibition of Smad2/3 phosphorylation and nuclear translocation. Among the active ingredients of S. chinensis extract, schisandrin B (SchB) most potently inhibited TGFβ1 signaling. SchB inhibited sustained phosphorylation and nuclear translocation of Smad2/3. Moreover, SchB suppressed TGFβ1-induced phosphorylation of p38 and JNK, which contributed to Smad2/3 inactivation. The present study is the first to demonstrate that S. chinensis extract and SchB inhibit TGFβ1 signaling. Our results may help future investigations to understand vascular fibrosis pathogenesis and to deve... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5444098 Sat, 12 Nov 2011 05:00:00 +0100 5444098 http://www.medworm.com/index.php?rid=5444097&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22100870%26dopt%3DAbstract Authors: Akool ES, Gauer S, Osman B, Doller A, Schulz S, Geiger H, Pfeilschifter J, Eberhardt W Abstract We previously demonstrated that the widely used immunosuppressive drugs cyclosporin A (CsA) and tacrolimus (FK506), independent of immunophilin binding, can activate profibrogenic transforming growth factor β (TGFβ)/Smad signaling cascades in rat renal mesangial cells (MC). Here we report that both peptidyl-prolyl cis/trans isomerase (PPIase) inhibitors activate the extracellular-signaling regulated kinase (ERK) a member of the mitogen activated protein kinase (MAPK) and induce a rapid and transient increase in ERK phosphorylation. The MEK inhibitor U0126, the reactive oxygen species (ROS) scavenger N-acetyl-cysteine (NAC), a cell-permeant superoxide dismutase (SOD) and stigma... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5444097 Wed, 09 Nov 2011 05:00:00 +0100 5444097 http://www.medworm.com/index.php?rid=5426354&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22093909%26dopt%3DAbstract This study provides new data demonstrating that at least the inverse agonist effect observed with >1μM concentrations of rimonabant in [(35)S]GTPγS binding assays is not mediated by the CB1 receptor in human brain. PMID: 22093909 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5426354 Mon, 07 Nov 2011 05:00:00 +0100 5426354 http://www.medworm.com/index.php?rid=5426356&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22062654%26dopt%3DAbstract Authors: Tucker TG, Milne AM, Fournel-Gigleux S, Fenner KS, Coughtrie MW Abstract The ATP-binding cassette (ABC) transporters breast cancer resistance protein (BCRP), multidrug resistance-associated protein 2 (MRP2), and P-glycoprotein (Pgp) are important in the distribution and elimination of many drugs and endogenous metabolites. Due to their membrane location and hydrophobicity it is difficult to generate purified protein standards to quantify these transporters in human tissues. The present study generated transporter proteins fused with the S-peptide of ribonuclease for use as standards in immunoquantification in human liver and small intestine. Quantification of the S•tag™, a 15 amino acid peptide, is based on the formation of a functional ribonuclease activity upon its h... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5426356 Mon, 31 Oct 2011 04:00:00 +0100 5426356 http://www.medworm.com/index.php?rid=5426358&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056620%26dopt%3DAbstract Authors: Wasowski C, Gavernet L, Barrios IA, Villalba ML, Pastore V, Samaja G, Enrique A, Bruno-Blanch LE, Marder M Abstract A set of sulfamides designed, synthesized and evaluated against maximal electroshock seizure (MES) and pentilenetetrazol (PTZ) tests with promising results, were tested for their affinity for the benzodiazepine binding site of the GABA(A) receptor. The most active compounds, N,N'-dicyclohexylsulfamide (7) and N,N'-diphenethylsulfamide (10), competitively inhibited the binding of [(3)H]-flunitrazepam to the benzodiazepine binding site with K(i)±SEM values of 27.7±4.5μM (n=3) and 6.0±1.2μM (n=3), respectively. The behavioral actions of these sulfamides, i.p. administered in mice, were examined in the plus-maze, hole-board and locomotor activity assays. Com... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5426358 Sat, 29 Oct 2011 04:00:00 +0100 5426358 http://www.medworm.com/index.php?rid=5426355&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067069%26dopt%3DAbstract Authors: De Clercq E Abstract The pre-exposure chemoprophylaxis (now commonly referred to as PrEP) of HIV infection has gained increased momentum, concomitantly with the successful use of combination drug regimens for the treatment of AIDS. A pivotal component in the current drug combination regimens for the treatment of AIDS as well as the ongoing PrEP trials is tenofovir disoproxil fumarate (TDF, Viread(®)) and its combination with emtricitabine (FTC). The combination of TDF with FTC has been marketed as Truvada(®). TDF and TDF/FTC has proven effective, if orally administered daily or intermittently, in the prevention of rectal simian human immunodeficiency virus (SHIV) infection in macaques. Topical tenofovir gel has proven effective in the prevention of HIV infection in women... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5426355 Sat, 29 Oct 2011 04:00:00 +0100 5426355 http://www.medworm.com/index.php?rid=5426357&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056621%26dopt%3DAbstract Authors: Jang TH, Lee SJ, Woo CH, Lee KJ, Jeon JH, Lee DS, Choi K, Kim IG, Kim YW, Lee TJ, Park HH Abstract Genotoxic stress induced apoptosis is mediated by the formation of PIDDosome, which is a caspase-2 activating complex composed of three protein components, PIDD, RAIDD, and caspase-2. Here, synthetic TAT-fused peptides designed by the structure of PIDD and RAIDD, TAT-Y814A and TAT-R147E, respectively, were produced and tested for their ability to inhibit PIDDosome formation in vitro as well as to attenuate genotoxic stress-induced apoptosis in human renal cancer cells. The results show that TAT-Y814A and TAT-R147E have the potential to inhibit formation of the PIDDosome in a dose-dependent manner. Furthermore, both peptides partially inhibit genotoxic stress mediated apoptosi... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5426357 Tue, 25 Oct 2011 04:00:00 +0100 5426357 http://www.medworm.com/index.php?rid=5382639&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22051078%26dopt%3DAbstract Authors: McGonigle P Abstract Neuropeptides play a crucial role in the normal function of the central nervous system and peptide receptors hold great promise as therapeutic targets for the treatment of several CNS disorders. In general, the development of peptide therapeutics has been limited by the lack of drug-like properties of peptides and this has made it very difficult to transform them into marketable therapeutic molecules. Some of these challenges include poor in vivo stability, poor solubility, incompatibility with oral administration, shelf stability, cost of manufacture. Recent technical advances have overcome many of these limitations and have led to rapid growth in the development of peptides for a wide range of therapeutic indications such as diabetes, cancer and pain... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382639 Tue, 25 Oct 2011 04:00:00 +0100 5382639 http://www.medworm.com/index.php?rid=5382640&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22044878%26dopt%3DAbstract Authors: Palmeira A, Helena Vasconcelos M, Paiva A, Fernandes MX, Pinto M, Sousa E Abstract For many pathologies, there is a crescent effort to design multiple ligands that interact with a wide variety of targets. 1-Aminated thioxanthone derivatives were synthesized and assayed for their in vitro dual activity as antitumor agents and P-glycoprotein (P-gp) inhibitors. The approach was based on molecular hybridization of a thioxanthone scaffold, present in known antitumor drugs, and an amine, described as an important pharmacophoric feature for P-gp inhibition. A rational approach using homology modeling and docking was used, to select the molecules to be synthesized by conventional or microwave-assisted Ullmann C-N cross-coupling reaction. The obtained aminated thioxanthones were hi... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382640 Sat, 22 Oct 2011 04:00:00 +0100 5382640 http://www.medworm.com/index.php?rid=5382645&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024132%26dopt%3DAbstract This study demonstrates for the first time that ivermectin induces P-glycoprotein overexpression through post-transcriptional mRNA stabilization, thus offering insight into the mechanism of reduced therapeutic efficacy and development of ivermectin-resistant parasites. PMID: 22024132 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382645 Tue, 18 Oct 2011 04:00:00 +0100 5382645 http://www.medworm.com/index.php?rid=5382644&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024133%26dopt%3DAbstract In this study we investigated the role of Mcl-1 in mitotic arrest-induced apoptosis. Vinblastine treatment of KB-3 cells initially resulted in a phosphatase-sensitive mobility shift in Mcl-1 and then subsequent loss of Mcl-1 protein expression which was prevented by MG132, suggesting that phosphorylation triggered proteosome-mediated degradation. Mcl-1 phosphorylation/degradation was a specific response to microtubule inhibition and did not occur in response to lethal concentrations of DNA damaging agents. Vinblastine treatment caused degradation of Mcl-1 in cells in which apoptosis was blocked by Bcl-xL overexpression, indicating that Mcl-1 degradation was not a consequence of apoptosis. A partial reversible phosphorylation of Mcl-1 was observed in synchronized cells traversing mitosis, w... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382644 Tue, 18 Oct 2011 04:00:00 +0100 5382644 http://www.medworm.com/index.php?rid=5382643&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22027220%26dopt%3DAbstract In this study we present cyclohexyl-[6-methyl-2-(4-morpholin-4-yl-phenyl)-imidazo[1,2-a]pyridin-3-yl]-amine (EP6), a novel imidazo[1,2-a]pyridine based compound and its characterization in several in vitro assays. EP6 suppresses 5-LO activity in intact polymorphonuclear leukocytes with an IC(50) value of 0.16μM and exhibits full inhibitory potency in cell free assays (IC(50) value of 0.05μM for purified 5-LO). The efficacy of EP6 was not affected by the redox tone or the concentration of exogenous AA, characteristic drawbacks known for the class of nonredox-type 5-LO inhibitors. Furthermore, EP6 suppressed 5-LO activity independently of the cell stimulus or the activation pathway of 5-LO contrary to what is known for some nonredox-type inhibitors. Using molecular modeling and site-direct... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382643 Tue, 18 Oct 2011 04:00:00 +0100 5382643 http://www.medworm.com/index.php?rid=5382642&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22027221%26dopt%3DAbstract In this study we have attempted to identify a possible molecular mechanism behind the above by investigating the effects of ebselen on Saccharomyces cerevisiae. Significant growth arrest was documented in yeast cells exposed to ebselen similar to that seen in presence of DNA damaging agents (including methyl methane sulfonate [MMS] and hydroxy urea [HU]). Furthermore, mutations in specific lysine residues in the histone H3 tail (H3 K56R) resulted in increased sensitivity of yeast cells to ebselen presumably due to alterations in post-translational modifications of histone proteins towards regulating replication and DNA damage repair. Our findings suggest that ebselen functions through activation of DNA damage response, alterations in histone modifications, activation of checkpoint kinase p... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382642 Tue, 18 Oct 2011 04:00:00 +0100 5382642 http://www.medworm.com/index.php?rid=5382641&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22027222%26dopt%3DAbstract Authors: de Wilt LH, Jansen G, Assaraf YG, van Meerloo J, Cloos J, Schimmer AD, Chan ET, Kirk CJ, Peters GJ, Kruyt FA Abstract The proteasome inhibitor bortezomib, registered for Multiple Myeloma treatment, is currently explored for activity in solid tumors including non-small cell lung cancer (NSCLC). Here we studied the proteasome-based mechanisms underlying intrinsic and acquired bortezomib resistance in NSCLC cells. Various NSCLC cell lines displayed differential intrinsic sensitivities to bortezomib. High basal chymotrypsin- and caspase-like proteasome activities correlated with bortezomib resistance in these cells. Next, via stepwise selection, acquired bortezomib resistant cells were obtained with 8-70-fold increased resistance. Cross-resistance was found to proteasome inhib... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382641 Tue, 18 Oct 2011 04:00:00 +0100 5382641 http://www.medworm.com/index.php?rid=5382648&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015635%26dopt%3DAbstract Authors: Jarvis IW, Meczes EL, Thomas HD, Edmondson RJ, Veal GJ, Boddy AV, Ottley CJ, Pearson DG, Tilby MJ Abstract Despite an increasing understanding of the molecular mechanisms by which platinum drug DNA adducts interact with cellular processes, the relationship between adduct formation in tumours and clinical response remains unclear. We have determined carboplatin-DNA adduct levels in biopsies removed from ovarian cancer patients following treatment. Reliability of DNA adduct measurements in tissues samples were assessed using experimental animals. Platinum-DNA adduct levels were measured using inductively coupled plasma mass spectrometry (ICP-MS) and plasma drug concentrations determined by atomic absorption spectrometry (AAS). Adduct levels in tissues and plasma pharmacokine... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382648 Fri, 14 Oct 2011 04:00:00 +0100 5382648 http://www.medworm.com/index.php?rid=5382647&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22020118%26dopt%3DAbstract Authors: Cheng YS, Tang YQ, Dai DZ, Dai Y Abstract We tested the hypothesis that aquaporin-4 (AQP4) knockout (KO) mice might exhibit abnormal Ca(2+) modulating proteins resulting from the exacerbation of pro-inflammatory factors in the heart. Downregulation of FKBP12.6, SERCA2a, and CASQ2 and calcium leak in diastole have been recognized as endpoints for assessing cardiac failure and arrhythmias. The AQP4 KO mice and wild-type (WT) mice were randomly divided into 3 groups, such as control, isoproterenol (ISO, β-receptor agonist) injected (1mg/kg, sc, 5d), and treated with aminoguanidine (AMG, 100mg/kg, po, a selective inhibitor of the iNOS) during the last 3d. RT-PCR, western blot and calcium transient measurements were conducted. The results demonstrated that the cardiac weight i... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382647 Fri, 14 Oct 2011 04:00:00 +0100 5382647 http://www.medworm.com/index.php?rid=5382646&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22020119%26dopt%3DAbstract This study shows that CYP26A1 and CYP26B1 are qualitatively similar RA hydroxylases with overlapping expression profiles. CYP26A1 has higher catalytic activity than CYP26B1 and seems to be responsible for metabolism of atRA in tissues that function as a barrier for atRA exposure. PMID: 22020119 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382646 Fri, 14 Oct 2011 04:00:00 +0100 5382646 http://www.medworm.com/index.php?rid=5382651&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22005520%26dopt%3DAbstract Authors: Avni D, Glucksam Y, Zor T Abstract The Phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002 (LY2), has been previously reported to inhibit nuclear factor κB (NFκB) activity, in a PI3K-independent mechanism. The goals of the current research were to determine the specificity of LY2 regarding NFκB subunits, and to identify relevant modulation of cytokine expression in LPS-stimulated macrophages. We found that LY2 specifically diminished the level of p50, but not p65, NFκB in the nucleus of LPS-stimulated mouse RAW264.7 macrophages and human THP-1 monocytes. This activity of LY2 was mimicked by its PI3K-inert analog LY303511 (LY3), but not by another PI3K inhibitor - wortmannin. We further show that LY2 inhibited LPS-induced IL-10 expression by RAW264.7 macrophages, i... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382651 Wed, 12 Oct 2011 04:00:00 +0100 5382651 http://www.medworm.com/index.php?rid=5382649&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015634%26dopt%3DAbstract This study examined chronic (once-a-day dosing for 8 weeks) effects of the DPP-4 inhibitor PKF-275-055 (1, 3, and 10mg/kg) on β-cell regeneration and plasma DPP-IV activity, intact GLP-1, glucose, and insulin after an oral glucose load in neonatal wistar rats injected with streptozotocin (STZ) (n2-STZ model), a recognized model of type 2 diabetes. In streptozotocin induced diabetic rats, PKF-275-055 (3, and 10mg/kg) significantly reduced glucose excursion during the oral glucose tolerance test conducted 2h and 10h after administration, with increases in plasma insulin and active glucagon-like peptide-1 (GLP-1) levels and significantly inhibited (> 50% inhibition) plasma DPP-IV activity during both the 1st and 2nd OGTT in diabetic rats. In contrast, PKF-275-055 (1-10mg/kg) did not cause... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382649 Wed, 12 Oct 2011 04:00:00 +0100 5382649 http://www.medworm.com/index.php?rid=5382654&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22005517%26dopt%3DAbstract In conclusion, our data indicate that Sam68 interacts with IRS-1 in basal conditions, and insulin increases the affinity between these two partners. PMID: 22005517 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382654 Mon, 10 Oct 2011 04:00:00 +0100 5382654 http://www.medworm.com/index.php?rid=5382653&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22005518%26dopt%3DAbstract Authors: Woo CC, Kumar AP, Sethi G, Tan KH Abstract Thymoquinone is an active ingredient isolated from Nigella sativa and has been investigated for its anti-oxidant, anti-inflammatory and anticancer activities in both in vitro and in vivo models since its first extraction in 1960s. Its anti-oxidant/anti-inflammatory effect has been reported in various disease models, including encephalomyelitis, diabetes, asthma and carcinogenesis. Moreover, thymoquinone could act as a free radical and superoxide radical scavenger, as well as preserving the activity of various anti-oxidant enzymes such as catalase, glutathione peroxidase and glutathione-S-transferase. The anticancer effect(s) of thymoquinone are mediated through different modes of action, including anti-proliferation, apoptosis ind... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382653 Mon, 10 Oct 2011 04:00:00 +0100 5382653 http://www.medworm.com/index.php?rid=5382658&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22000995%26dopt%3DAbstract We report here that oxidative stress and nitrosative stress occur in pancreas and lung in acute pancreatitis and the co-treatment with oxypurinol and pentoxifylline prevents oxidative stress in both tissues. Oxypurinol was effective in preventing glutathione oxidation, whereas pentoxifylline abrogated glutathione depletion. This latter effect was independent of TNF-α since glutathione depletion occurred in mice deficient in TNF-α or its receptors after induction of pancreatitis. The beneficial effects of oxypurinol in the inflammatory response may also be ascribed to a partial inhibition of MEK1/2 activity. Pentoxifylline markedly reduced the expression of Icam1 and iNos induced by TNF-αin vitro in AR42J cells. Oxidative stress significantly contributes to the TNF-α-induced up-regulati... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382658 Sat, 08 Oct 2011 04:00:00 +0100 5382658 http://www.medworm.com/index.php?rid=5382652&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22005519%26dopt%3DAbstract Authors: Jingushi K, Takahashi-Yanaga F, Yoshihara T, Shiraishi F, Watanabe Y, Hirata M, Morimoto S, Sasaguri T Abstract We previously reported that differentiation-inducing factor-1 (DIF-1), a morphogen in Dictyostelium discoideum, inhibits the proliferation of human cancer cell lines by inducing β-catenin degradation and suppressing the Wnt/β-catenin signaling pathway. To determine whether β-catenin degradation is essential for the effect of DIF-1, we examined the effect of DIF-1 on human colon cancer cell lines (HCT-116, SW-620 and DLD-1), in which the Wnt/β-catenin signaling pathway is constitutively active. DIF-1 strongly inhibited cell proliferation and arrested the cell cycle in the G(0)/G(1) phase via the suppression of cyclin D1 expression at mRNA and protein levels wi... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382652 Sat, 08 Oct 2011 04:00:00 +0100 5382652 http://www.medworm.com/index.php?rid=5382650&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22008592%26dopt%3DAbstract Authors: Murad JP, Espinosa EV, Ting HJ, Khasawneh FT Abstract There is considerable interest in discovering novel antiplatelet approaches with an enhanced safety profile. To this end, in our efforts to define new targets for antithrombotic activity, we investigated the utility of antibodies which recognize the ligand binding domains of the platelet thromboxane A(2) receptor (TPR). We hypothesized that an antibody (abbreviated as C-EL2Ab), which interacts with the C-terminus of the second extracellular loop (C-EL2; i.e., ligand binding domain) of TPR exhibits antagonistic activity. Our findings demonstrate that C-EL2Ab did indeed inhibit TPR-mediated platelet aggregation. However, it was devoid of any apparent effects on aggregation triggered by ADP or the thrombin receptor activat... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382650 Sat, 08 Oct 2011 04:00:00 +0100 5382650 http://www.medworm.com/index.php?rid=5382657&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001310%26dopt%3DAbstract In this study, experiments with reporter constructs showed that the prototypical Nrf2 activator tert-butyl hydroquinone (t-BHQ) induces CBR3 promoter activity in cultures of HepG2 (2.7-fold; p<0.05) and MCF-7 cells (22-fold; p<0.01). Computational searches identified a conserved ARE in the distal CBR3 promoter region ((-2698)ARE). Deletion of this ARE from a 4212-bp CBR3 promoter construct impacted basal promoter activity and induction of promoter activity in response to treatment with t-BHQ. Deletion of (-2698)ARE also impacted the induction of CBR3 promoter activity in cells overexpressing Nrf2. Electrophoretic mobility shift assays (EMSA) demonstrated increased binding of specific protein complexes to (-2698)ARE in nuclear extracts from t-BHQ treated cells. The presence of Nrf2 in... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382657 Wed, 05 Oct 2011 04:00:00 +0100 5382657 http://www.medworm.com/index.php?rid=5382656&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001311%26dopt%3DAbstract Authors: Henkel A, Kather N, Mönch B, Northoff H, Jauch J, Werz O Abstract Lipophilic extracts of gum resins of Boswellia species (BSE) are used in folk medicine to treat various inflammatory disorders and infections. The molecular background of the beneficial pharmacological effects of such extracts is still unclear. Various boswellic acids (BAs) have been identified as abundant bioactive ingredients of BSE. Here we report the identification of defined BAs as direct inhibitors of lipopolysaccharide (LPS) functionality and LPS-induced cellular responses. In pull-down experiments, LPS could be precipitated using an immobilized BA, implying direct molecular interactions. Binding of BAs to LPS leads to an inhibition of LPS activity which was observed in vitro using a modified limulus... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382656 Wed, 05 Oct 2011 04:00:00 +0100 5382656 http://www.medworm.com/index.php?rid=5382655&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001442%26dopt%3DAbstract Authors: Graudins A, Little MJ, Pineda SS, Hains PG, King GF, Broady KW, Nicholson GM Abstract The venom of the European black widow spider Latrodectus tredecimguttatus (Theridiidae) contains several high molecular mass (110-140kDa) neurotoxins that induce neurotransmitter exocytosis. These include a vertebrate-specific α-latrotoxin (α-LTX-Lt1a) responsible for the clinical symptoms of latrodectism and numerous insect-specific latroinsectoxins (LITs). In contrast, little is known about the expression of these toxins in other Latrodectus species despite the fact that envenomation by these spiders induces a similar clinical syndrome. Here we report highly conserved α-LTX, α-LIT and δ-LIT sequence tags in Latrodectus mactans, Latrodectus hesperus and Latrodectus hasselti venoms u... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382655 Wed, 05 Oct 2011 04:00:00 +0100 5382655 http://www.medworm.com/index.php?rid=5382665&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983034%26dopt%3DAbstract Authors: Zhong H, Sánchez C, Caron MG Abstract The serotonin transporter (SERT) functions to transport serotonin (5-HT) from the extracellular space into neurons to maintain homeostatic control of 5-HT. It is the molecular target for selective serotonin reuptake inhibitor (SSRI) antidepressants. Preclinical research has shown that some SERT inhibitors can bind to two distinct binding sites on the SERT, a primary high affinity binding site and a low affinity allosteric binding site. Mutational studies of the SERT and computational modeling methods with escitalopram resulted in the identification of key amino acid residues important for the function of the allosteric binding site. While this allosteric binding site appears to influence the clinical efficacy of escitalopram under phy... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382665 Sat, 01 Oct 2011 04:00:00 +0100 5382665 http://www.medworm.com/index.php?rid=5382681&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983032%26dopt%3DAbstract Authors: Schwaninger AE, Meyer MR, Barnes AJ, Kolbrich-Spargo EA, Gorelick DA, Goodwin RS, Huestis MA, Maurer HH Abstract The R- and S-enantiomers of racemic 3,4-methylenedioxymethamphetamine (MDMA) exhibit different dose-concentration curves. In plasma, S-MDMA was eliminated at a higher rate, most likely due to stereoselective metabolism. Similar data were shown in various in vitro experiments. The aim of the present study was the in vivo investigation of stereoselective elimination of MDMA's phase I and phase II metabolites in human urine following controlled oral MDMA administration. Urine samples from 10 participants receiving 1.0 and 1.6mg/kg MDMA separated by at least one week were analyzed blind by liquid chromatography-high resolution-mass spectrometry and gas chromatograph... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382681 Thu, 29 Sep 2011 04:00:00 +0100 5382681 http://www.medworm.com/index.php?rid=5382678&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21983033%26dopt%3DAbstract Authors: Clarion L, Schindler M, de Weille J, Lolmède K, Laroche-Clary A, Uro-Coste E, Robert J, Mersel M, Bakalara N Abstract 7β-Hydroxycholesterol cytotoxicity has been shown in vivo and in vitro to be dependent on the accumulation of its esters. We show in our study, using a detergent-free raft preparation and LC/MS lipid content analysis, that membrane microdomains isolated from 7β-hydroxycholesterol-treated C6 cells have a reduced cholesterol: cholesterol ester ratio and accumulate 7keto-hydroxycholesterol, 7β-hydroxycholesterol and 7β-hydroxycholesterol esters. These modifications in lipid content are accompanied by a redistribution of flotillin-1 in the lipid rafts. Transient increases of AMPK phosphorylation and mitochondrial activity during the first 12h of 7β-hydrox... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5382678 Thu, 29 Sep 2011 04:00:00 +0100 5382678 http://www.medworm.com/index.php?rid=5301653&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21971583%26dopt%3DAbstract In conclusion, our results indicate the utility of the combination of VE-465 and vincristine as a potential therapy for myeloid leukemia. PMID: 21971583 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5301653 Thu, 29 Sep 2011 04:00:00 +0100 5301653 http://www.medworm.com/index.php?rid=5301652&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21978643%26dopt%3DAbstract In conclusion, since TDP1 alone can account for mild levels of camptothecin resistance, repair of topoisomerase I-mediated DNA damage likely occurs through redundant pathways mainly implicating BRCA1 and XRCC1, but not RAD17 and PARP1. These findings may be relevant to define novel therapeutic strategies. PMID: 21978643 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5301652 Thu, 29 Sep 2011 04:00:00 +0100 5301652 http://www.medworm.com/index.php?rid=5301654&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21968035%26dopt%3DAbstract This study was designed to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to a lethal dose of sarin (GB) vapor. Male Göttingen minipigs were subjected to: air exposure, GB vapor exposure, or pretreatment with Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection 24h prior to exposure to 4.1mg/m(3) of GB vapor for 60min. Electrocardiograms (ECG), electroencephalograms (EEG), and pupil size were recorded throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB present. Untreated animals exposed to GB vapor exhibited cardiac abnormalities and generalized seizures, ultimately succumbing to respiratory failure. Pretreatm... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5301654 Sat, 24 Sep 2011 04:00:00 +0100 5301654 http://www.medworm.com/index.php?rid=5283233&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21964343%26dopt%3DAbstract Authors: Viola G, Bortolozzi R, Hamel E, Moro S, Brun P, Castagliuolo I, Ferlin MG, Basso G Abstract We previously demonstrated that MG-2477 (3-cyclopropylmethyl-7-phenyl-3H-pyrrolo[3,2-f]quinolin-9(6H)-one) inhibits the growth of several cancer cell lines in vitro. Here we show that MG-2477 inhibited tubulin polymerization and caused cells to arrest in metaphase. The detailed mechanism of action of MG-2477 was investigated in a non-small cell lung carcinoma cell line (A549). Treatment of A549 cells with MG-2477 caused the cells to arrest in the G2/M phase of the cell cycle, with a concomitant accumulation of cyclin B. Moreover, the compound induced autophagy, which was followed at later times by apoptotic cell death. Autophagy was detected as early as 12h by the conversion of micr... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5283233 Thu, 22 Sep 2011 04:00:00 +0100 5283233 http://www.medworm.com/index.php?rid=5283232&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21964344%26dopt%3DAbstract Authors: Ellison I, Richie JP Abstract Glutathione (GSH) plays numerous critical protective roles in the erythrocyte and GSH turnover is likely an important factor in regulating susceptibility to oxidative stress and toxins. Efflux of glutathione disulfide (GSSG) from erythrocytes is an important component in the regulation of GSH levels; however, little is known of the mechanisms involved. We hypothesize that multidrug resistance associated protein 1 (MRP1) is responsible, in part, for GSSG transport from erythrocytes. To test this, we determined the levels of MRP1 protein in erythrocyte membranes from healthy adults and compared them with intracellular levels of GSH. MRP1 levels varied substantially from person to person and were inversely correlated with levels of GSH (r=-0.39, ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5283232 Thu, 22 Sep 2011 04:00:00 +0100 5283232 http://www.medworm.com/index.php?rid=5283231&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21964345%26dopt%3DAbstract Authors: Castañeda S, Roman-Blas JA, Largo R, Herrero-Beaumont G Abstract Osteoarthritis (OA), the most common form of arthritis, is a debilitating and progressive disease that has become a major cause of disability and impaired quality of life in the elderly. OA is considered an organ disease that affects the whole joint, where the subchondral bone (SB) plays a crucial role. Regardless of whether SB alterations precede cartilage damage or appear during the evolution of the disease, SB is currently recognised as a key target in OA treatment. In fact, bone abnormalities, especially increased bone turnover, have been detected in the early evolution of some forms of OA. Systemic osteoporosis (OP) and OA share a paradoxical relationship in which both high and low bone mass conditions ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5283231 Thu, 22 Sep 2011 04:00:00 +0100 5283231 http://www.medworm.com/index.php?rid=5266492&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21946083%26dopt%3DAbstract Authors: Li C, Lu N, Qi Q, Li F, Ling Y, Chen Y, Qin Y, Li Z, Zhang H, You Q, Guo Q Abstract Cell adhesion plays an important role in the steps of cancer metastasis. Regulation of cell-cell (intercellular) and cell-matrix adhesion is a promising strategy for cancer progression. Gambogic acid is a xanthone derived from the resin of the Chinese plant Garciania hanburyi, with potent anti-metastasis activity on highly metastatic cells. The aim of this study was to investigate the function and mechanism of gambogic acid on tumor adhesion. We found that gambogic acid strongly inhibited the adhesion of human cancer cells to fibronectin. This inhibition was associated with the deformation of focal adhesion complex, which was mediated by suppressing the expression of integrin β1 and integr... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5266492 Sat, 17 Sep 2011 04:00:00 +0100 5266492 http://www.medworm.com/index.php?rid=5266491&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21946084%26dopt%3DAbstract In conclusion, insulin deficiency induces abnormal increase in intestinal disaccharidase activities and expression under diabetic states. Insulin plays an essential role in regulation disaccharidase activities and expression, at least in part, via the MAPK-dependent pathway. PMID: 21946084 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5266491 Sat, 17 Sep 2011 04:00:00 +0100 5266491 http://www.medworm.com/index.php?rid=5266490&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21946085%26dopt%3DAbstract Authors: Chen G, Davies MA Abstract One of the foremost challenges in oncology is developing improved therapies for preventing and treating metastases to the brain. Recent research in this area is bringing about a shift in the understanding of brain metastases. Previously, the occurrence and poor outcomes associated with brain metastases have been largely attributed to the exclusion of anticancer drugs from the brain by the blood-brain barrier (BBB). However, studies in multiple tumor types have also demonstrated that brain metastases have significant molecular differences from primary tumors and extracranial metastases. These molecular differences may not only promote the formation of brain metastases, but they may also contribute to these tumors' poor responsiveness to therapies.... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5266490 Sat, 17 Sep 2011 04:00:00 +0100 5266490 http://www.medworm.com/index.php?rid=5266498&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21930116%26dopt%3DAbstract In conclusion, EcN supplementation to minocycline treatment improves the recovery of the intestinal damage and prevents the reactivation of experimental colitis. PMID: 21930116 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5266498 Fri, 16 Sep 2011 04:00:00 +0100 5266498 http://www.medworm.com/index.php?rid=5266497&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933664%26dopt%3DAbstract Authors: Wittmann HJ, Seifert R, Strasser A Abstract Numerous competitive radioligand binding studies revealed significant differences between human and guinea pig histamine H(1)-receptors (hH(1)R and gpH(1)R), e.g. for the partial H(1)R agonist phenoprodifen. But until now, there are only few studies with regard to binding kinetics at H(1)R. Previous studies from our group revealed an influence of the exchange of N-terminus and E2-loop between hH(1)R and gpH(1)R onto affinity of phenoprodifen to H(1)R (Strasser A, Wittmann HJ, Seifert R, J Pharmacol Exp Ther 326:783-791, 2008). The aim of this study was, therefore, to examine the impact of the N-terminus and the E2-loop on binding kinetics of the H(1)R. The wild type hH(1)R and gpH(1)R and the chimeric h(gpE2)H(1)R (E2-loogp from ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5266497 Fri, 16 Sep 2011 04:00:00 +0100 5266497 http://www.medworm.com/index.php?rid=5266496&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933665%26dopt%3DAbstract In this study we have investigated the effect of two major regulators of hepatic energy homeostasis, the transcriptional coactivator, peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α) and the NAD-dependent deacetylase protein, sirtuin 1 (SIRT1) on PXR expression and function. Fasting induces PXR expression in liver. Furthermore, glucagon and PGC-1α overexpression upregulate PXR expression level in mouse primary hepatocytes suggesting that PGC-1α, in addition to coactivation of PXR, also transcriptionally regulates PXR gene. Knockdown of peroxisome proliferator-activated receptor α by siRNA attenuates PGC-1α mediated induction of PXR mRNA. PGC-1α overexpression alone has no effect on cytochrome P450 (CYP) 3A11 expression but potentiates induction by pregnenolo... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5266496 Fri, 16 Sep 2011 04:00:00 +0100 5266496 http://www.medworm.com/index.php?rid=5266495&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945484%26dopt%3DAbstract Authors: Skinbjerg M, Sibley DR, Javitch JA, Abi-Dargham A Abstract Positron Emission Tomography (PET) has been used for more than three decades to image and quantify dopamine D(2) receptors (D(2)R) in vivo with antagonist radioligands but in the recent years agonist radioligands have also been employed. In vitro competition studies have demonstrated that agonists bind to both a high and a low-affinity state of the D(2)Rs, of which the high affinity state reflects receptors that are coupled to G-proteins and the low-affinity state reflects receptors uncoupled from G-proteins. In contrast, antagonists bind with uniform affinity to the total pool of receptors. Results of these studies led to the proposal that D(2)Rs exist in high and low-affinity states for agonists in vivo and spark... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5266495 Fri, 16 Sep 2011 04:00:00 +0100 5266495 http://www.medworm.com/index.php?rid=5266494&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945668%26dopt%3DAbstract Authors: Wu ZZ, Chow KP, Kuo TC, Chang YS, Chao CC Abstract Expression of the oncogenic latent membrane protein 1 (LMP1) of Epstein-Barr virus is involved in the pathogenesis of nasopharyngeal carcinoma (NPC) and lymphoma. In previous studies, we found that expression of LMP1 was sufficient to transform BALB/c-3T3 cells. In contrast, other studies have shown that LMP1 induces apoptosis in a NF-κB-dependent manner and also inhibits the growth of tumors in mice, thereby indicating that LMP1 may produce various biological effects depending on the biological and cellular context. Still, the mechanism underlying the pro-apoptotic activity of LMP1 remains unclear. In the present study, we found that LMP1 inhibits the expression of NAPA, an endoplasmic reticulum SNARE protein that posses... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5266494 Fri, 16 Sep 2011 04:00:00 +0100 5266494 http://www.medworm.com/index.php?rid=5266493&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945989%26dopt%3DAbstract Authors: Inoue T, Suzuki Y, Ra C Abstract The green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) has various biological activities, including anti-inflammatory, anti-neoplastic, anti- and pro-apoptotic, and neuroprotective effects. Although these are often associated with increased intracellular reactive oxygen species (ROS) and Ca(2+) levels, their involvement in biological effects is poorly understood. Here we report that EGCG induces cytokine production in mast cells via Ca(2+) influx and ROS generation. EGCG at concentrations of ≥50μM induced interleukin-13 and tumor necrosis factor-α production in RBL-2H3 and bone marrow-derived mast cells. The effects were dependent on extracellular Ca(2+), and EGCG induced Ca(2+) release from intracellular stores and Ca(2+) inf... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5266493 Fri, 16 Sep 2011 04:00:00 +0100 5266493 http://www.medworm.com/index.php?rid=5266489&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21946086%26dopt%3DAbstract Authors: Greco KV, Iqbal AJ, Rattazzi L, Nalesso G, Moradi-Bidhendi N, Moore AR, Goldring MB, Dell'accio F, Perretti M Abstract Osteoarthritis is a highly prevalent and disabling disease for which we do not have a cure. The identification of suitable molecular targets is hindered by the lack of standardized, reproducible and convenient screening assays. Following extensive comparisons of a number of chondrocytic cell lines, culture conditions, and readouts, we have optimized an assay utilizing C-28/I2, a chondrocytic cell line cultured in high-density micromasses. Utilizing molecules with known effects on cartilage (e.g. IL-1β, TGFβ1, BMP-2), we have exploited this improved protocol to (i) evoke responses characteristic of primary chondrocytes; (ii) assess the pharmacodynamics of... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5266489 Fri, 16 Sep 2011 04:00:00 +0100 5266489 http://www.medworm.com/index.php?rid=5108334&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741955%26dopt%3DAbstract Authors: Mullane K Over the last 30 years, scientific research into asthma has focused almost exclusively on one component of the disorder - airway inflammation - as being the key underlying feature. These studies have provided a remarkably detailed and comprehensive picture of the events following antigen challenge that lead to an influx of T cells and eosinophils in the airways. Indeed, in basic research, even the term "asthma" has become synonymous with a T helper 2 cell-mediated disorder. From this cascade of cellular activation processes and mediators that have been identified it has been possible to pinpoint critical junctures for therapeutic intervention, leading experimentalists to produce therapies that are very effective in decreasing airway inflammation in animal models. Man... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108334 Wed, 10 Aug 2011 04:55:49 +0100 5108334 http://www.medworm.com/index.php?rid=5108332&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21745459%26dopt%3DAbstract Authors: Mullane K The prevalence of asthma continues to rise. Current drugs provide symptomatic relief to some, but not all, patients. Despite the need for new therapeutics, and a huge research effort, only four novel agents from two classes of drugs - the antileukotrienes and an anti-IgE antibody - have been approved in the last 30 years. This review highlights three particular issues that contribute to the challenge of identifying new therapeutics. First is an over-reliance on animal models of allergy to define targets and expectations of efficacy that has met with poor translation to the clinical setting. While sensitivity to particular aeroallergens is one key risk factor for asthma, atopy and asthma are not synonymous, and while about half of adult asthmatics are atopic the incid... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108332 Wed, 10 Aug 2011 04:55:40 +0100 5108332 http://www.medworm.com/index.php?rid=5108307&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21801714%26dopt%3DAbstract Authors: Kundu R, Dasgupta S, Biswas A, Bhattacharya S, Pal BC, Bhattacharya S, Rao PG, Barua NC, Bordoloi MJ, Bhattacharya S Accumulation of bilirubin, primarily because of its insolubility, has been found to be associated with liver diseases including jaundice. Free bilirubin is insoluble; its glucuronidation by bilirubin-UGT enzyme (UGT1A1) makes it soluble and eliminates it through urine and faeces. Taking CCl(4) induced rat liver dysfunction model, we demonstrated that suppression of UGT1A1 activity in rat liver increased serum bilirubin level which could be reversed by carlinoside (Cln), a flavone glycoside. Although Cln is a flavone compound, it escaped self-glucuronidation in the intestine and readily absorbed. Kinetic study of microsomal UGT1A1 from HepG2 cells suggested that ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108307 Tue, 26 Jul 2011 23:00:00 +0100 5108307 http://www.medworm.com/index.php?rid=5108297&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820419%26dopt%3DAbstract Authors: Rufini S, Lena AM, Cadot B, Mele S, Amelio I, Terrinoni A, Desideri A, Melino G, Candi E The transcription factor p63 plays pivotal roles in epidermal barrier formation and in embryonic development. The protein structures of TAp63 and ΔNp63α isoforms include a C-terminal steril alpha-motif (SAM) involved in protein-protein interaction. Identification of p63 SAM domain interactors could lead to the explanation of novel mechanisms of regulation of p63 activity, possibly relevant in the physiological role of p63 and in genetic disorders associated with mutations of the p63 gene. In this work, we have performed a biochemical analysis of p63 SAM domain preferences in lipid binding. We have identified the ganglioside GM1 as a high affinity interactor, capable of modulating p63 tra... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108297 Tue, 26 Jul 2011 23:00:00 +0100 5108297 http://www.medworm.com/index.php?rid=5108296&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820420%26dopt%3DAbstract Authors: Song MK, Salam NK, Roufogalis BD, Huang TH The peroxisome proliferator activated receptor-γ (PPAR-γ) is involved in the pathogenesis of diabetic retinopathy. Diabetic retinopathy is a preventable microvascular diabetic complication that damages human retinal pigment epithelial cells. Taurine is abundant in the fruit of Lycium barbarum (Goji Berry), and is reportedly beneficial for diabetic retinopathy. However, the mechanism of its action is unknown. Hence, we have investigated the mechanism of action of an extract from L. barbarum on a model of diabetic retinopathy, the retinal ARPE-19 cell line, and identified the receptor function of taurine, an active component of L. barbarum (Goji Berry) extract, which is potentially responsible for the protective effect on diabetic ret... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108296 Tue, 26 Jul 2011 23:00:00 +0100 5108296 http://www.medworm.com/index.php?rid=5108295&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820421%26dopt%3DAbstract Authors: Johnson MA, Winquist RJ Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD), involve a poorly understood and complex immune response to both the biota of the human gut and the gut itself. The role of the gut biota in human health has been ill defined and attitudes toward the intestinal flora have ranged from judging them largely irrelevant to declaring them a human organ system. A better way to view the intestinal flora is as a group of evolutionarily self-interested species that form large, potentially interbreeding populations that utilize human beings as a series of semi-isolated habitats, like islands in an archipelago. Here we propose that the imposition of modern sanitation and hygiene standards has drastically attenuated the connection between the "islands"... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108295 Tue, 26 Jul 2011 23:00:00 +0100 5108295 http://www.medworm.com/index.php?rid=5108294&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21820422%26dopt%3DAbstract Authors: Park B, Sung B, Yadav VR, Chaturvedi MM, Aggarwal BB Triptolide, a diterpene triepoxide, from the Chinese herb Tripterygium wilfordii Hook.f, exerts its anti-inflammatory and immunosuppressive activities by inhibiting the transcription factor nuclear factor-κB (NF-κB) pathway, through a mechanism not yet fully understood. We found that triptolide, in nanomolar concentrations, suppressed both constitutive and inducible NF-κB activation, but did not directly inhibit binding of p65 to the DNA. The diterpene did block TNF-induced ubiquitination, phosphorylation, and degradation of IκBα, the inhibitor of NF-κB and inhibited acetylation of p65 through suppression of binding of p65 to CBP/p300. Triptolide also inhibited the IκBα kinase (IKK) that activates NF-κB and phosphor... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108294 Tue, 26 Jul 2011 23:00:00 +0100 5108294 http://www.medworm.com/index.php?rid=5108299&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21819972%26dopt%3DAbstract This study expands current knowledge on mechanisms of how DMXAA acts as a potent anti-tumor agent in murine system and also provides useful information for further study on the mechanism of action of this potential anti-tumor compound in human macrophages. PMID: 21819972 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108299 Mon, 25 Jul 2011 23:00:00 +0100 5108299 http://www.medworm.com/index.php?rid=5108306&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803024%26dopt%3DAbstract Authors: Peroni RN, Di Gennaro SS, Hocht C, Chiappetta DA, Rubio MC, Sosnik A, Bramuglia GF The oral bioavailability of the antiretroviral efavirenz (EFV) undergoes high inter and intra-individual variability, this fact supporting its therapeutic drug monitoring. Previously, it was demonstrated that the encapsulation of EFV within polymeric micelles increases the oral bioavailability of the drug. The breast cancer resistant protein (BCRP, ABCG2) is known to be inhibited by EFV in vitro. Since ABCG2 is profusely expressed in the gastrointestinal tract, the aim of the present work was to thoroughly investigate whether the intestinal permeability of EFV is modulated by ABCG2. The functional role of ABCG2 in mediating the transport of EFV at the intestinal level was consistent with the fol... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108306 Fri, 22 Jul 2011 23:00:00 +0100 5108306 http://www.medworm.com/index.php?rid=5108305&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803025%26dopt%3DAbstract Authors: Joshi JP, Brown NE, Griner SE, Nahta R Resistance to the anti-HER2 monoclonal antibody trastuzumab is a major problem in the treatment of HER2-overexpressing metastatic breast cancer. Growth differentiation factor 15 (GDF15), which is structurally similar to TGF beta, has been reported to stimulate phosphorylation of HER2. We tested the hypothesis that GDF15-mediated phosphorylation of HER2 reduces the sensitivity of HER2-overexpressing breast cancer cell lines to trastuzumab. Gene microarray analysis, real-time PCR, and ELISA were used to assess GDF15 expression. Growth inhibition and proliferation assays in response to pharmacologic inhibitors of HER2, TGF beta receptor, or Src were performed on cells stimulated with recombinant human GDF15 or stable GDF15 transfectants. Wes... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108305 Fri, 22 Jul 2011 23:00:00 +0100 5108305 http://www.medworm.com/index.php?rid=5108304&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803026%26dopt%3DAbstract Authors: Riganti C, Pinto H, Bolli E, Belisario DC, Calogero RA, Bosia A, Cavallo F The widely used anticholesterolemic drugs statins decrease the synthesis of cholesterol and the isoprenylation and activity of small G-proteins such as Ras and Rho, the effectors of which are often critical in cell proliferation. Thanks to this property, it has been hypothesized that statins may have anti-tumor activities. We investigated this issue in BALB-neuT mice, which developed Her2/neu-positive mammary cancers with 100% penetrance, and in TUBO cells, a cell line established from these tumors. Contrary to the mammary glands of BALB/c mice, the tumor tissue from BALB-neuT animals had constitutively activated Ras and ERK1/2. These were reduced by the oral administration of atorvastatin, but the stat... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108304 Fri, 22 Jul 2011 23:00:00 +0100 5108304 http://www.medworm.com/index.php?rid=5108303&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803027%26dopt%3DAbstract In conclusion, our investigations collectively provide strong evidence that VCN-2 is effective against CaP progression along with indicating that VCN-2 and DTL co-administration is more effective than either of the single agents in androgen-independent prostate cancer. PMID: 21803027 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108303 Fri, 22 Jul 2011 23:00:00 +0100 5108303 http://www.medworm.com/index.php?rid=5108302&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803028%26dopt%3DAbstract Authors: Wong YC, Sim MK, Lee KO Although clinical studies suggested that blockade of the renin-angiotensin system may prevent diabetes, the mechanism is uncertain. As a follow-up to an earlier study, we investigated how des-aspartate-angiotensin-1 (DAA-1) and its metabolite, angiotensin IV (Ang-IV) improved glucose tolerance in diet-induced hyperglycaemic mice. Male C57BL/6J mice were fed a high-fat-high-sucrose (HFD) or normal (ND) diet for 52 weeks. HFD animals were orally administered either DAA-I (600nmol/kg/day), Ang-IV (400nmol/kg/day) or distilled water. Body weight, blood glucose and insulin were measured fortnightly. Inflammatory and insulin signalling transducers that are implicated in hyperglycaemia were analyzed in skeletal muscles at 52 weeks. HFD animals developed hyperg... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108302 Fri, 22 Jul 2011 23:00:00 +0100 5108302 http://www.medworm.com/index.php?rid=5108301&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21803029%26dopt%3DAbstract Authors: Chiaravalli J, Fontan E, Fsihi H, Coic YM, Baleux F, Véron M, Agou F Aberrant and constitutive NF-κB activation are frequently reported in numerous tumor types, making its inhibition an attractive target for the treatment of certain cancers. NEMO (NF-κB essential modulator) is the crucial component of the canonical NF-κB pathway that mediates IκB kinase (IKK) complex activation. IKK activation resides in the ability of the C-terminal domain of NEMO to properly dimerize and interact with linear and K63-linked polyubiquitin chains. Here, we have identified a new NEMO peptide inhibitor, termed UBI (ubiquitin binding inhibitor) that derives from the NOA/NUB/UBAN ubiquitin binding site located in the CC2-LZ domain of NEMO. UBI specifically inhibits the NF-κB pathway at the IK... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108301 Fri, 22 Jul 2011 23:00:00 +0100 5108301 http://www.medworm.com/index.php?rid=5108298&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21819973%26dopt%3DAbstract Authors: Park HS, Jun DY, Han CR, Woo HJ, Kim YH Exposure of human Jurkat T cells to MG132 caused apoptosis along with upregulation of Grp78/BiP and CHOP/GADD153, activation of JNK and p38MAPK, activation of Bak, mitochondrial membrane potential (Δψm) loss, cytochrome c release, activation of caspase-12, -9, -3, -7, and -8, cleavage of Bid and PARP, and DNA fragmentation. However, these MG132-induced apoptotic events, with the exceptions of upregulation of Grp78/BiP and CHOP/GADD153 and activation of JNK and p38MAPK, were abrogated by overexpression of Bcl-xL. Pretreatment with the pan-caspase inhibitor z-VAD-fmk prevented MG132-induced apoptotic caspase cascade, but allowed upregulation of Grp78/BiP and CHOP/GADD153 levels, activation of JNK and p38MAPK, Δψm loss, and cleavage of ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108298 Fri, 22 Jul 2011 23:00:00 +0100 5108298 http://www.medworm.com/index.php?rid=5108300&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21806975%26dopt%3DAbstract Authors: Simboeck E, Ribeiro JD, Teichmann S, Di Croce L Cellular senescence is the biological consequence of aging. However, the same mechanisms that provoke senescence during aging have been proven to act in tumor suppression and thus to occur in premalignant cells. All the diverse aspects of the senescent phenotype, as are observed for many other cell fates, arise from alterations of the chromatin architecture. Relatively little is known overall about the changes in chromatin structure, and which regulatory networks are implicated in these. Major insight into the epigenetic contributions to senescence has been gained by studying the regulation of the INK4-ARF locus. Activation of the tumor suppressors encoded by this locus leads to an irreversible cell cycle exit. Importantly, epige... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108300 Thu, 21 Jul 2011 23:00:00 +0100 5108300 http://www.medworm.com/index.php?rid=5108321&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21784060%26dopt%3DAbstract In this study, we show that p67phox is constitutively phosphorylated in resting human neutrophils and that neutrophil stimulation with PMA further enhanced this phosphorylation. Inhibition of the constitutively active serine/threonine phosphatases type 1 and type 2A (PP1/2A) by calyculin A resulted in the enhancement of p67phox phosphorylation. Constitutive and calyculin A-induced phosphorylation of p67phox was completely inhibited by the protein tyrosine kinase inhibitor genistein and partially inhibited by the MEK1/2 inhibitor PD98059, but was unaffected by GF109203X, wortmannin and SB203580, inhibitors of PKC, PI3K and p38MAP kinase, respectively. Two-dimensional phosphopeptide mapping revealed that constitutive and calyculin A-induced p67phox phosphorylation occurred on the same major ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108321 Wed, 20 Jul 2011 23:00:00 +0100 5108321 http://www.medworm.com/index.php?rid=5108320&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21784061%26dopt%3DAbstract In this study, YM155 was administered to a panel of cell lines and the effects of YM155 on Bcl-2 family members were analyzed. Our results show that YM155 strikingly downregulates Mcl-1 in a broad spectrum of cancer cell lines and that the Mcl-1 modulation occurs at the transcriptional level, independently of survivin modulation or caspase activity. Furthermore, analysis of the contribution of Mcl-1 or survivin downregulation to YM155-induced cell death in vitro showed that knockdown of Mcl-1 sensitizes cells to YM155-induced cytotoxicity. Finally, our data demonstrate that downregulation of Mcl-1 by YM155 synergistically lowers the threshold of Bcl-2 family member inhibitor ABT-263-induced cell death. Our findings reveal a novel mechanism by which survivin-independent Mcl-1 suppression pl... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108320 Wed, 20 Jul 2011 23:00:00 +0100 5108320 http://www.medworm.com/index.php?rid=5108322&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782803%26dopt%3DAbstract Authors: Paolini M, De Biasi M Smoking is responsible for over 400,000 premature deaths in the United States every year, making it the leading cause of preventable death. In addition, smoking-related illness leads to billions of dollars in healthcare expenditures and lost productivity annually. The public is increasingly aware that successfully abstaining from smoking at any age can add years to one's life and reduce many of the harmful effects of smoking. Although the majority of smokers desire to quit, only a small fraction of attempts to quit are actually successful. The symptoms associated with nicotine withdrawal are a primary deterrent to cessation and they need to be quelled to avoid early relapse. This review will focus on the neuroadaptations caused by chronic nicotine exposur... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108322 Tue, 19 Jul 2011 23:00:00 +0100 5108322 http://www.medworm.com/index.php?rid=5108319&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787753%26dopt%3DAbstract Authors: Hoffmann J, Junker H, Schmieder A, Venz S, Brandt R, Multhoff G, Falk W, Radons J Human pancreatic cancer is currently one of the fifth-leading causes of cancer-related mortality with a 5-year survival rate of less than 5%. Since pancreatic carcinoma is largely refractory to conventional therapies, there is a strong medical need for the development of novel and innovative therapeutic strategies. Increasing evidence suggests an association of carcinogenesis and chronic inflammation. Because IL-1 plays a crucial role in inflammation-associated carcinogenesis, we analyzed the biological effects of IL-1 and its modulation by the chemopreventive green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) in the human pancreatic adenocarcinoma cell line Colo357. Proinflammatory IL-6 ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108319 Tue, 19 Jul 2011 23:00:00 +0100 5108319 http://www.medworm.com/index.php?rid=5108318&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787754%26dopt%3DAbstract Authors: Francione LM, Fisher PR The bewildering complexity of the relationship between genotype and phenotype in human mitochondrial diseases has delayed an understanding of the related cytopathological mechanisms. To explore the relationship between mitochondrial dysfunction in Dictyostelium discoideum and the related cytopathologies, we determined whether the phenotypic outcomes were similar regardless of which D. discoideum mitochondrial gene was targeted for disruption. The disruption of the mitochondrial genes resulted in a similar pattern of phenotypes to those caused by other mitochondrial defects. These include impairment of phototaxis, multicellular development and growth on plates and in liquid medium. As the reduced growth rates could have been due to defective phagocytic o... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108318 Tue, 19 Jul 2011 23:00:00 +0100 5108318 http://www.medworm.com/index.php?rid=5108317&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787755%26dopt%3DAbstract Authors: Wu J, Lukas RJ Nicotinic acetylcholine receptors (nAChRs) warrant attention, as they play many critical roles in brain and body function and have been implicated in a number of neurological and psychiatric disorders, including nicotine dependence. nAChRs are composed as diverse subtypes containing specific combinations of genetically-distinct subunits and that have different functional properties, distributions, and pharmacological profiles. There had been confidence that the rules that define ranges of assembly partners for specific subunits were well-established, especially for the more prominent nAChR subtypes. However, we review here some newer findings indicating that nAChRs having largely the same, major subunits exist as isoforms with unexpectedly different properties. ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108317 Tue, 19 Jul 2011 23:00:00 +0100 5108317 http://www.medworm.com/index.php?rid=5108316&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787756%26dopt%3DAbstract Authors: Khor TO, Huang Y, Wu TY, Shu L, Lee J, Kong AN Prostate cancer (PCa) is one of the most deadly malignancies among men in the United States. Although localized prostate cancer can be effectively treated via surgery or radiation, metastatic disease is usually lethal. Recent evidence suggests that the development and progression of human prostate cancer involves complex interplay between epigenetic alterations and genetic defects. We have recently demonstrated that Nrf2, a master regulator of cellular antioxidant defense systems, was epigenetically silenced during the progression of prostate tumorigenesis in TRAMP mice. The aim of this study is to investigate the potential of curcumin (CUR), a dietary compound that we have reported to be able to prevent the development of prostat... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108316 Tue, 19 Jul 2011 23:00:00 +0100 5108316 http://www.medworm.com/index.php?rid=5108315&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787757%26dopt%3DAbstract Authors: Reymond JL, van Deursen R, Bertrand D The activity of ligand gated channels is crucial for proper brain function and dysfunction of a single receptor subtype have led to neurological impairments ranging from benign to major diseases such as epilepsy, startle diseases, etc. Molecular biology and crystallography allowed the characterization at the atomic scale of the first four transmembrane ligand gated channels and of proteins sharing a high degree of homology with the neurotransmitter-binding domain. Gaining an adequate knowledge of the structural features of the ligand binding pocket led to the possibilities of developing virtual screening based approaches and probing in silico the docking of very large numbers of molecules. Development of new computing tools further extende... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108315 Tue, 19 Jul 2011 23:00:00 +0100 5108315 http://www.medworm.com/index.php?rid=5108314&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787758%26dopt%3DAbstract Authors: Verhelst K, Verstrepen L, Carpentier I, Beyaert R Despite its small size, ubiquitin is one of the most versatile signaling molecules in the cell and affects distinct cellular processes. It forms the building block of a repertoire of posttranslational modifications of cellular proteins, ranging from the attachment of a single ubiquitin to ubiquitin chains of different linkage. Proteins that contain ubiquitin chain-specific ubiquitin-binding domains recognize different types of ubiquitination and determine the mode of signaling of modified proteins. Polyubiquitin chains were thought to be formed only by the conjugation of the ubiquitin C-terminal Gly to one of the seven internal Lys residues of another ubiquitin. However, the C-terminal Gly was recently shown to also link to the... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108314 Tue, 19 Jul 2011 23:00:00 +0100 5108314 http://www.medworm.com/index.php?rid=5108313&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787759%26dopt%3DAbstract In conclusion, plated primary human hepatocytes are useful as an in vitro model for OATP1B1/1B3-mediated uptake studies, but the culture time may substantially change the uptake kinetics. PMID: 21787759 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108313 Tue, 19 Jul 2011 23:00:00 +0100 5108313 http://www.medworm.com/index.php?rid=5108312&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787760%26dopt%3DAbstract Authors: Pierre S, Bats AS, Coumoul X Son of Sevenless (SOS) was discovered in Drosophila melanogaster. Essential for normal eye development in Drosophila, SOS has two human homologues, SOS1 and SOS2. The SOS1 gene encodes the Son of Sevenless 1 protein, a Ras and Rac guanine nucleotide exchange factor. This protein is composed of several important domains. The CDC25 and REM domains provide the catalytic activity of SOS1 towards Ras and the histone fold DH/PH (Dbl homology and Pleckstrin homology) domains function, in tandem, to stimulate GTP/GDP exchange for Rac. In contrast to Ras, there have been few studies that implicate SOS1 in human disease and, initially, less attention was given to this gene. However, mutations in SOS1 have been reported recently in Noonan syndrome and in type... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108312 Tue, 19 Jul 2011 23:00:00 +0100 5108312 http://www.medworm.com/index.php?rid=5108311&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787761%26dopt%3DAbstract Authors: Rufini A, Barlattani A, Docimo R, Velletri T, Niklison-Chirou MV, Agostini M, Melino G Recent findings have shown that the development of teeth involves a complex sequence of molecular events in which the p53 family member p63 is involved. Indeed, mice lacking p63 do not have teeth and humans bearing mutations in p63 suffer developmental syndromes that affect tooth morphology and number. Several isoforms of p63 have been described: the use of two different promoters produces longer TAp63 isoforms, or shorter, 5' truncated isoforms known as ΔNp63. The 3' end of primary transcripts is then subject to alternative splicing resulting in three additional isoforms: alpha (α), beta (β) and gamma (γ). Tooth development relies mainly on the activity of the N-terminally truncated ΔN... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108311 Tue, 19 Jul 2011 23:00:00 +0100 5108311 http://www.medworm.com/index.php?rid=5108310&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787762%26dopt%3DAbstract Authors: Di Paola R, Impellizzeri D, Salinaro AT, Mazzon E, Bellia F, Cavallaro M, Cornelius C, Vecchio G, Calabrese V, Rizzarelli E, Cuzzocrea S l-Carnosine is an endogenously synthesized dipeptide composed of beta-alanine and l-histidine. It acts as a free radical scavenger and possesses antioxidant properties. l-Carnosine reduces proinflammatory and profibrotic cytokines such as transforming growth factor-beta (TGF-beta), interleukin (IL)-1, and tumor necrosis factor (TNF)-alpha in different experimental settings. In the present study, we investigated the efficacy of l and d-carnosine on the animal model of spinal cord injury (SCI). The spinal cord was exposed via a four-level T5-T8 laminectomy and SCI was produced by extradural compression of the spinal cord at level T6-T7 using an... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108310 Tue, 19 Jul 2011 23:00:00 +0100 5108310 http://www.medworm.com/index.php?rid=5108309&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787763%26dopt%3DAbstract Authors: Barbieri F, Würth R, Favoni RE, Pattarozzi A, Gatti M, Ratto A, Ferrari A, Bajetto A, Florio T Malignant pleural mesothelioma (MPM) is an aggressive chemotherapy-resistant cancer. Up-regulation of epidermal growth factor receptor (EGFR) plays an important role in MPM development and EGFR-tyrosine kinase inhibitors (TKIs) may represent novel therapeutic options. We tested the effects of the EGFR TKIs gefitinib and erlotinib and TKIs targeted to other growth factors (VEGFR and PDGFR), in comparison to standard antineoplastic agents, in two human MPM cell lines, IST-Mes2 and ZL55. All drugs showed IC(50) values in the micromolar range: TKIs induced cytostatic effects at concentrations up to the IC(50,) while conventional drug growth-inhibitory activity was mainly cytotoxic. More... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108309 Tue, 19 Jul 2011 23:00:00 +0100 5108309 http://www.medworm.com/index.php?rid=5108308&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21798250%26dopt%3DAbstract Authors: Bush K, Pucci MJ Antibiotic resistance issues necessitate the continued discovery and development of new antibacterial agents. Efforts are ongoing in two approaches to find new compounds that are effective against antibiotic-resistant pathogens. These efforts involve modification of existing classes including fluoroquinolones, tetracyclines, aminoglycosides, and β-lactams and identification of inhibitors against previously unexploited antibacterial targets. Examples of both approaches are described here with emphasis on compounds in late pre-clinical or clinical stages of development. PMID: 21798250 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108308 Tue, 19 Jul 2011 23:00:00 +0100 5108308 http://www.medworm.com/index.php?rid=5108326&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763293%26dopt%3DAbstract This article summarizes recent advances involving the discovery, signaling pathways and functions of ABA in animals. PMID: 21763293 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108326 Thu, 07 Jul 2011 23:00:00 +0100 5108326 http://www.medworm.com/index.php?rid=5108329&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763290%26dopt%3DAbstract In conclusion, EA reduces the damage in a rat model of Crohn's disease, alleviates the oxidative events and returns pro-inflammatory proteins expression to basal levels probably through MAPKs and NF-κB signalling pathways. PMID: 21763290 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108329 Wed, 06 Jul 2011 23:00:00 +0100 5108329 http://www.medworm.com/index.php?rid=5108328&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763291%26dopt%3DAbstract Authors: Parri HR, Hernandez CM, Dineley KT Aberrant amyloid-β peptide (Aβ) accumulation along with altered expression and function of nicotinic acetylcholine receptors (nAChRs) stand prominently in the etiology of Alzheimer's disease (AD). Since the discovery that Aβ is bound to α7 nAChRs under many experimental settings, including post-mortem AD brain, much effort has been expended to understand the implications of this interaction in the disease milieu. This research update will review the current literature on the α7 nAChR-Aβ interaction in vitro and in vivo, the functional consequences of this interaction from sub-cellular to cognitive levels, and discuss the implications these relationships might have for AD therapies. PMID: 21763291 [PubMed - as supplied by publisher] ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108328 Wed, 06 Jul 2011 23:00:00 +0100 5108328 http://www.medworm.com/index.php?rid=5108325&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763684%26dopt%3DAbstract Authors: Maiani E, Diederich M, Gonfloni S A complex regulatory network of signaling pathways safeguards genome integrity following DNA damage. When double strand breaks occur several enzymes and mediators are recruited to the sites of lesion to release a network of DNA repair processes referred to as DNA damage response (DDR). c-Abl interacts in the nucleus with several proteins implicated in distinct aspects of DNA repair. This suggests that c-Abl may be involved in the regulation of double strand break repair. The involvement of c-Abl in DNA repair mechanisms came into the spotlight in female germ cells under genotoxic stress. Recent findings have implicated c-Abl in a cisplatin-induced signaling pathway eliciting death of immature oocytes. Pharmacological inhibition of c-Abl by Ima... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108325 Wed, 06 Jul 2011 23:00:00 +0100 5108325 http://www.medworm.com/index.php?rid=5108324&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763685%26dopt%3DAbstract Authors: Lee CH, Zhu C, Malysz J, Campbell T, Shaughnessy T, Honore P, Polakowski J, Gopalakrishnan M Nicotinic acetylcholine receptors (nAChRs) function as ligand-gated ion channels activated by the neurotransmitter acetylcholine. Gene knockout and antisense studies coupled with pharmacological studies with nAChR agonists have documented a role of α4β2 nAChR activation in analgesia. ABT-594, for the first time, provided clinical validation to the nAChR agonist pharmacology as a novel mechanism for treatment of pain. However, ABT-594 was poorly tolerated at the efficacious doses, particularly with respect to the side effects of nausea and emesis, which is thought to be mediated by activation of the ganglionic-type (α3-containing) nAChRs. An alternate approach is to selectively modul... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108324 Wed, 06 Jul 2011 23:00:00 +0100 5108324 http://www.medworm.com/index.php?rid=5108323&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782802%26dopt%3DAbstract Authors: Chateauvieux S, Grigorakaki C, Morceau F, Dicato M, Diederich M Erythropoietin (EPO) is a glycoprotein that is mainly produced in the adult kidney, and it was initially highlighted for its action on the hematopoietic system. Moreover, EPO is also expressed in several non-hematopoietic tissues, where it plays a role in the protection from apoptosis and inflammation due to hypoxia, toxicity or injury. These protective effects are mainly known and studied in cardioprotection and neuroprotection but are also reported in retina degeneration, auditory injury and pancreatic-related diseases. The tissue protective effect of EPO is mainly mediated through the interaction with the heterodimeric receptor EPOR/βcR. Human recombinant EPO (HuREPO), which has been developed to treat anemia,... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108323 Wed, 06 Jul 2011 23:00:00 +0100 5108323 http://www.medworm.com/index.php?rid=5108330&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21762680%26dopt%3DAbstract Authors: Zeng F, Lu JJ, Zhou XF, Wang YJ Alzheimer's disease (AD), the most common form of dementia, is characterized by the deposition of amyloid plaques, accumulation of fibrillary tangles in neurons, neurite degeneration, loss of neurons, and a progressive loss of cognitive function. The pathogenesis of AD is not fully understood, and no strong disease-modifying therapies are currently available. Recent studies suggest that the pan-neurotrophin receptor, p75NTR, is a critical factor involved in the pathogenesis of AD. In this review, we have discussed the roles of p75NTR in the production of amyloid-beta (Aβ), neuronal death, neurite degeneration, tau hyperphosphorylation, cell cycle re-entry and cognition decline in AD, and proposed that p75NTR is a potential target for the develo... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108330 Mon, 04 Jul 2011 23:00:00 +0100 5108330 http://www.medworm.com/index.php?rid=5108327&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763292%26dopt%3DAbstract Authors: Ha YM, Ham SA, Kim YM, Lee YS, Kim HJ, Seo HG, Lee JH, Park MK, Chang KC High mobility group box (HMGB)-1 plays an important role in sepsis-associated death in experimental studies. Heme oxygenase-1 (HO-1) inducers were reported to reduce HMGB1 release in experimental sepsis. Previously, we reported on the importance of the β1-adrenergic receptor and protein kinase A pathway in the regulation of HO-1 expression by isoproterenol (ISO) in RAW 264.7 cells. We investigated whether ISO reduces HMGB1 release in LPS-activated RAW 264.7 cells and improves survival rate in septic mice due to HO-1 induction. ISO concentration-dependently increased HO-1 via Nrf-2 translocation and inhibited release of HMGB1 through the β(1)-adrenergic receptor (β(1)-AR) in LPS-activated RAW 264.7 cell... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108327 Mon, 04 Jul 2011 23:00:00 +0100 5108327 http://www.medworm.com/index.php?rid=5108336&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741371%26dopt%3DAbstract Authors: Hayashi S, Sumi Y, Ueno N, Murase A, Takada J Cyclooxygenase (COX) has been considered as a significant pharmacological target because of its pivotal roles in the prostaglandin biosynthesis and following cascades that lead to various (patho)physiological effects. Non-steroidal anti-inflammatory drugs (NSAIDs) that suppress COX activities have been used clinically for the treatment of fever, inflammation, and pain; however, nonselective COX inhibitors exhibit serious side-effects such as gastrointestinal damage because of their inhibitory activities against COX-1. Thus, COX-1 is constitutive and expressed ubiquitously and serves a housekeeping role, while COX-2 is inducible or upregulated by inflammatory/injury stimuli such as interleukin-1β, tumor necrosis factor-α, and lipo... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108336 Fri, 01 Jul 2011 23:00:00 +0100 5108336 http://www.medworm.com/index.php?rid=5108335&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741954%26dopt%3DAbstract Authors: Wallace TL, Porter RH A promising drug target currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (α7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the α7nAChR has many properties that make it an attractive therapeutic target. The α7nAChR is a ligand gated ion channel that has particularly high permeability to Ca(2+) and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The α7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling casc... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108335 Fri, 01 Jul 2011 23:00:00 +0100 5108335 http://www.medworm.com/index.php?rid=5108333&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741956%26dopt%3DAbstract Authors: Nicolini V, Cassinelli G, Cuccuru G, Bongarzone I, Petrangolini G, Tortoreto M, Mondellini P, Casalini P, Favini E, Zaffaroni N, Zunino F, Lanzi C Emerging evidence suggests that Ret oncoproteins expressed in medullary thyroid cancer (MTC) might evade the pro-apoptotic function of the dependence receptor proto-Ret by directly impacting the apoptosis machinery. Identification of the molecular determinants of the interplay between Ret signaling and apoptosis might provide a relevant contribution to the optimization of Ret-targeted therapies. Here, we describe the cross-talk between Ret-M918T oncogenic mutant responsible for type 2B multiple endocrine syndrome (MEN2B), and components of death receptor-mediated extrinsic apoptosis pathway. In the human MEN2B-type MTC cell line MZ-... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108333 Fri, 01 Jul 2011 23:00:00 +0100 5108333 http://www.medworm.com/index.php?rid=5108331&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21745460%26dopt%3DAbstract Authors: Imanishi J, Morita Y, Yoshimi E, Kuroda K, Masunaga T, Yamagami K, Kuno M, Hamachi E, Aoki S, Takahashi F, Nakamura K, Miyata S, Ohkubo Y, Mutoh S Nonsteroidal anti-inflammatory drugs (NSAIDs) are now understood to fall into one of two agent classes in clinical use. Traditional NSAIDs inhibit both cyclooxygenases-1 and 2 (COX-1, 2), which act as key enzymes catalyzing the same reaction in the production of prostaglandins (PGs), while the second class of NSAIDs selectively inhibit COX-2. Inhibition of the inducible COX-2 isoform is believed to be responsible for the therapeutic effects of NSAIDs, such as anti-inflammatory, analgesic, and antipyretic effects, while COX-1 inhibition results in side-effects on the gastrointestinal (GI) system. In the present study, however, we cha... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108331 Fri, 01 Jul 2011 23:00:00 +0100 5108331 http://www.medworm.com/index.php?rid=5108337&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21740894%26dopt%3DAbstract Authors: Tuesta LM, Fowler CD, Kenny PJ Tobacco smoking is one of the leading causes of disease and premature death in the United States. Nicotine is considered the major reinforcing component in tobacco smoke responsible for tobacco addiction. Nicotine acts in the brain through the neuronal nicotinic acetylcholine receptors (nAChRs). The predominant nAChR subtypes in mammalian brain are those containing α4 and β2 subunits. The α4β2 nAChRs, particularly those located in the mesoaccumbens dopamine pathway, play a key role in regulating the reinforcing properties of nicotine. Considering that twelve mammalian nAChR subunits have been cloned, it is likely that nAChRs containing subunits in addition to, or other than, α4 and β2 also play a role in the tobacco smoking habit. Consisten... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5108337 Tue, 28 Jun 2011 23:00:00 +0100 5108337 http://www.medworm.com/index.php?rid=5011984&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21736870%26dopt%3DAbstract This study is aimed at investigating the pathway involved in activation of PKD in platelets. We show that PKD2 is the major isoform of PKD that is expressed in human as well as murine platelets but not PKD1 or PKD3. PKD2 activation induced by AYPGKF was abolished with a G(q) inhibitor YM-254890, but was not affected by Y-27632, a RhoA/p160ROCK inhibitor, indicating that PKD2 activation is G(q)-, but not G(12/13)-mediated Rho-kinase dependent. Calcium-mediated signals are also required for activation of PKD2 as dimethyl BAPTA inhibited its phosphorylation. GF109203X, a pan PKC inhibitor abolished PKD2 phosphorylation but Go6976, a classical PKC inhibitor had no effect suggesting that novel PKC isoforms are involved in PKD2 activation. Importantly, Rottlerin, a non-selective PKCδ inhibitor,... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011984 Mon, 27 Jun 2011 23:00:00 +0100 5011984 http://www.medworm.com/index.php?rid=5011983&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21736871%26dopt%3DAbstract Authors: Letchworth SR, Whiteaker P Recent progress has been made in the understanding of the anatomical distribution, composition, and physiological role of nicotinic acetylcholine receptors containing the α6 subunit. Extensive study by many researchers has indicated that a collection of α6-containing receptors representing a nicotinic sub-family is relevant in preclinical models of nicotine self-administration and locomotor activity. Due to a number of technical difficulties, the state of the art of in vitro model systems expressing α6-containing receptors has lagged behind the state of knowledge of native α6 nAChR subunit composition. Several techniques, such as the expression of chimeric and concatameric α6 subunit constructs in oocytes and mammalian cell lines have been emplo... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011983 Mon, 27 Jun 2011 23:00:00 +0100 5011983 http://www.medworm.com/index.php?rid=5011982&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21736872%26dopt%3DAbstract This study provides the first evidence that HSP70 accelerates gastric ulcer healing. The results also suggest that both the HSP70 produced prior to ulcer formation and released from damaged cells, and the HSP70 produced after ulcer formation are involved in this accelerated healing process. PMID: 21736872 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011982 Mon, 27 Jun 2011 23:00:00 +0100 5011982 http://www.medworm.com/index.php?rid=5011981&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21736873%26dopt%3DAbstract Authors: Anshu A, Thomas S, Agarwal P, Ibarra-Rivera TR, Pirrung MC, Schönthal AH The proteasome has been recognized as a druggable target in cancer cells, and this has led to searches for pharmacologic agents that target this cellular organelle for cancer therapeutic purposes. Syrbactins are a group of microbial metabolites consisting of two related families, the glidobactins and the syringolins. Some members of this group have revealed cytotoxic efficacy in tumor cells, and more recently it was discovered that they exert proteasome-inhibitory function. Based on this therapeutic promise and to gain further understanding of their molecular modes of action, we chemically synthesized de-novo three novel syrbactin analogs and characterized their proteasome-inhibitory and in vitro anti-ne... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011981 Mon, 27 Jun 2011 23:00:00 +0100 5011981 http://www.medworm.com/index.php?rid=5011993&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718690%26dopt%3DAbstract Authors: Araud T, Graw S, Berger R, Lee M, Neveu E, Bertrand D, Leonard S The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. Schizophrenic patients have low levels of α7*nAChR, as measured by binding of the ligand [(125)I]-α-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and els... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011993 Sun, 26 Jun 2011 23:00:00 +0100 5011993 http://www.medworm.com/index.php?rid=5011994&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21708139%26dopt%3DAbstract Authors: Kota D, Sanjakdar S, Marks MJ, Khabour O, Alzoubi K, Damaj MI Tobacco smoking during adolescence has become a prominent preventable health problem faced in the United States. Addictive properties of smoking are thought to have a pronounced effect at a young age, thereby increasing vulnerability to a life-long addiction and decreasing the likelihood of smoking cessation during adulthood. Learning and memory involvement in nicotine reward was assessed in early adolescent (PND 28-34) and adult (PND 70+) male ICR mice by conducting conditioning sessions of nicotine (0.5mg/kg) acquisition at varying time-spans, and evaluating extinction and reinstatement of nicotine preference using Conditioned Place Preference. Acquisition studies resulted in a significant preference for nicotine ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011994 Thu, 23 Jun 2011 23:00:00 +0100 5011994 http://www.medworm.com/index.php?rid=5011991&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723852%26dopt%3DAbstract Authors: Devallière J, Charreau B A better knowledge of the process by which inflammatory extracellular signals are relayed from the plasma membrane to specific intracellular sites is a key step to understand how inflammation develops and how it is regulated. This review focuses on Lnk (SH2B3) a member, with SH2B1 and SH2B2, of the SH2B family of adaptor proteins that influences a variety of signaling pathways mediated by Janus kinase and receptor tyrosine kinases. SH2B adaptor proteins contain conserved dimerization, pleckstrin homology, and SH2 domains. Initially described as a regulator of hematopoiesis and lymphocyte differentiation, Lnk now emerges as a key regulator in hematopoeitic and non hematopoeitic cells such as endothelial cells (EC) moderating growth factor and cytokine ... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011991 Thu, 23 Jun 2011 23:00:00 +0100 5011991 http://www.medworm.com/index.php?rid=5011990&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723853%26dopt%3DAbstract Authors: Yum S, Choi J, Hong S, Park MH, Lee J, Ha NC, Jung Y Prolyl 4-hydroxylases (P4Hs), such as collagen prolyl-4-hydroxylases (CPHs) and hypoxia inducible factor prolyl-4-hydroxylases (HPHs), have recently been recognized as promising drug targets for the treatment of fibrotic and ischemic diseases. CPHs and HPHs catalyze identical metabolic reactions, yet lead to quite different physiological consequences, collagen synthesis and the regulation of oxygen homeostasis. Selective modulation of the two enzymes should provide a therapeutic benefit upon pharmacotherapy. In an in vitro VHL capture assay, hydroxylation of the 19mer HIF peptide (corresponding to HIF-1α residues 556-574) by HPH-2 was effectively prevented by nitric oxide (NO) donors, (±)-S-nitroso-N-acetylpenicillamine (S... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011990 Thu, 23 Jun 2011 23:00:00 +0100 5011990 http://www.medworm.com/index.php?rid=5011987&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726541%26dopt%3DAbstract In this study, the contribution of the redox partners cytochrome P450 reductase (CPR) and cytochrome b5 to the substrate dependent activity of CYP2C8.3 (R139K, K399R) was investigated in human liver microsomes (HLMs) and Escherichia coli expressed recombinant CYP2C8 proteins using amodiaquine, paclitaxel, rosiglitazone and cerivastatin as probe substrates. For recombinant CYP2C8.3, clearance values were two- to five-fold higher compared to CYP2C8.1. CYP2C8.3's higher k(cat) seems to be dominated by a higher, but substrate specific affinity, towards cytochrome b5 and CPR (K(D) and K(m,red)) which resulted in increased reaction coupling. A stronger binding affinity of ligands to CYP2C8.3, based on a two site binding model, in conjunction with a five fold increase in amplitude of heme spin ch... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011987 Thu, 23 Jun 2011 23:00:00 +0100 5011987 http://www.medworm.com/index.php?rid=5011986&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726542%26dopt%3DAbstract Authors: Gray K, Bennett M Atherosclerosis leading to cardiovascular disease is the leading cause of death among western populations. Atherosclerosis in characterised by the development of a fibrofatty lesion that consists of a diverse cell population, including inflammatory cells that create an intensely oxidising environment within the vessel. Coupled with normal replication, the local intracellular and extracellular environment causes damage to cellular DNA that is recognised and repaired by the DNA damage response (DDR) pathway. The role of DNA damage and the resulting deregulation of 'normal' cellular behaviour and subsequent loss of cell cycle control checkpoints have been widely studied in cancer. However, despite the extensive evidence for DNA damage in atherosclerosis, it is o... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011986 Thu, 23 Jun 2011 23:00:00 +0100 5011986 http://www.medworm.com/index.php?rid=5011985&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21726543%26dopt%3DAbstract Authors: Patwardhan RS, Checker R, Sharma D, Kohli V, Priyadarsini KI, Sandur SK The aim of this study was to investigate whether dimethoxycurcumin (DiMC), a synthetic curcumin analogue having higher metabolic stability over curcumin, could exhibit anti-inflammatory activity in murine and human lymphocytes. Both curcumin and DiMC suppressed mitogen as well as antigen driven proliferation of murine splenic lymphocytes. Further, mitogen and antigen-stimulated cytokine (IL-2, IL-4, IL-6 and IFN-γ) secretion by T cells was also abrogated by curcumin and DiMC. Interestingly, curcumin and DiMC suppressed B cell proliferation induced by lipopolysaccharide. Curcumin and DiMC also inhibited Con A-induced activation of early and late T cell activation markers. They scavenged basal reactive oxyg... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011985 Thu, 23 Jun 2011 23:00:00 +0100 5011985 http://www.medworm.com/index.php?rid=5011989&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723854%26dopt%3DAbstract Authors: Campbell NR, Fernandes CC, John D, Lozada AF, Berg DK The hippocampus is one of only two regions in the adult brain where neurons are generated in significant numbers throughout the lifetime of the animal. Numerous studies have demonstrated that these adult-born neurons are essential for optimal cognitive function with unimpaired memory formation and retrieval. The extent to which adult-born neurons survive through an early "critical period" and become integrated into functional networks has been shown to depend on the richness of stimulation they receive during these formative stages. The dentate gyrus in the hippocampus - home of the adult-born neurons - receives extensive cholinergic innervation, and newly generated neurons in the adult hippocampus express substantial numbe... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011989 Wed, 22 Jun 2011 23:00:00 +0100 5011989 http://www.medworm.com/index.php?rid=5011988&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723855%26dopt%3DAbstract Authors: Poraj-Kobielska M, Kinne M, Ullrich R, Scheibner K, Kayser G, Hammel KE, Hofrichter M The synthesis of hydroxylated and O- or N-dealkylated human drug metabolites (HDMs) via selective monooxygenation remains a challenging task for synthetic organic chemists. Here we report that aromatic peroxygenases (APOs; EC 1.11.2.1) secreted by the agaric fungi Agrocybe aegerita and Coprinellus radians catalyzed the H(2)O(2)-dependent selective monooxygenation of diverse drugs, including acetanilide, dextrorphan, ibuprofen, naproxen, phenacetin, sildenafil and tolbutamide. Reactions included the hydroxylation of aromatic rings and aliphatic side chains, as well as O- and N-dealkylations and exhibited different regioselectivities depending on the particular APO used. At best, desired HDMs w... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011988 Wed, 22 Jun 2011 23:00:00 +0100 5011988 http://www.medworm.com/index.php?rid=5011992&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718691%26dopt%3DAbstract In this study, we initially characterized the effects of several imidazoquinolinamine allosteric modulators (LUF5999, LUF6000 and LUF6001) on the human A(3) AR stably expressed in CHO cells using a cyclic AMP functional assay. These modulators were found to affect efficacy and potency of the agonist Cl-IB-MECA differently. LUF5999 (2-cyclobutyl derivative) enhanced efficacy but decreased potency. LUF6000 (2-cyclohexyl derivative) enhanced efficacy without affecting potency. LUF6001 (2-H derivative) decreased both efficacy and potency. We further compared the agonist enhancing effects of LUF6000 in several other A(3) AR-mediated events. It was shown that although LUF6000 behaved somewhat differently in various signaling pathways, it was more effective in enhancing the effects of low-efficac... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011992 Mon, 20 Jun 2011 23:00:00 +0100 5011992 http://www.medworm.com/index.php?rid=5011995&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704606%26dopt%3DAbstract Authors: Sastry SK, Elferink LA In recent years, targeted therapies for receptor tyrosine kinases (RTKs) have shown initial promise in the clinical setting for the treatment of several tumors driven by these oncogenic signaling pathways. Unfortunately, clinical relapse due to acquired resistance to these molecular therapeutics is common. An improved understanding of how tumors bypass the inhibitory effects of RTK-targeted therapies has revealed a rich myriad of possible mechanisms for acquired resistance. Protein tyrosine phosphatases (PTPs) can function as oncogenes or tumor suppressors to either enhance or suppress RTK signaling. Recent studies suggest that the loss or gain of function of PTP's can significantly impinge on RTK signaling during tumor progression. Here we review the in... Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011995 Thu, 16 Jun 2011 23:00:00 +0100 5011995 http://www.medworm.com/index.php?rid=5011998&cid=s_34543_13_f&fid=34543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704021%26dopt%3DAbstract Authors: Sobolewski C, Viry E, Legrand N, Muller F, Morceau F, Diederich M PMID: 21704021 [PubMed - as supplied by publisher] (Source: Biochemical Pharmacology) Biochemical Pharmacology journals http://www.medworm.com/rss/comments.php?id=5011998 Wed, 15 Jun 2011 23:00:00 +0100 5011998