exp Mol Med
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Effect of the membrane permeable cAMP analog, dibutyryl cAMP, on caspase-dependent apoptosis, inflammatory gene expression, and graft survival in acute cardiac allograft rejection.
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This study was designed to investigate the effects of cAMP on immune regulation and apoptosis during acute rat cardiac allograft rejection. We found that the production of immune markers such as inflammatory cytokines (interlukin-1b, interlukin-6, and tumor necrosis factor-a), inducible nitric oxide synthase (iNOS) expression, and nitric oxide (NO) production, was significantly increased in the blood and transplanted hearts of allograft recipients, but not of isograft controls. These increases were effectively suppressed by the administration of the membrane permeable cAMP analog dibutyryl cAMP (db-cAMP). Administration of...
Source: exp Mol Med - November 4, 2009 Category: Molecular Biology Authors: Lee JY, Kim JH, Chae G, Ha KS, Kwon YG, Kim YM Tags: Exp Mol Med Source Type: journals
Further understanding of fat biology: Lessons from a fat fly.
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Obesity is a leading risk factor for insulin resistance, hypertension, hyperlipidemia, and cardiovascular complications, collectively referred to as metabolic diseases. Given the prevalence of obesity and its associated medical problems, new strategies are required to prevent or treat obesity and obesity-related metabolic effects. Here we summarize contributors of obesity, and molecular mechanisms controlling adipogenesis from studies in mammalian systems. We also discuss the possibilities of using Drosophila as a genetic model system to advance our understanding of players in fat biology.
PMID: 19887892 [PubMed - ...
Source: exp Mol Med - November 4, 2009 Category: Molecular Biology Authors: Hong JW, Park KW Tags: Exp Mol Med Source Type: journals
PTH accelerates decompensation following left ventricular hypertrophy.
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In this study, pressure overload-induced left ventricular hypertrophy (LVH) was induced in mice by transverse aortic banding (TAB) for 2 weeks. We subsequently evaluated the effects of a 2-week treatment with PTH or saline on compensated LVH. After another 4 weeks, the hearts of the mice were analyzed by echocardiography, histology, and molecular biology. Echocardiography showed that hearts of the PTH-treated mice have more severe failing phenotypes than the saline-treated mice following TAB with a greater reduction in fractional shortening and left ventricular posterior wall thickness and with a greater increase in left v...
Source: exp Mol Med - November 4, 2009 Category: Molecular Biology Authors: Cha H, Jeong HJ, Jang SP, Kim JY, Yang DK, Oh JG, Park WJ Tags: Exp Mol Med Source Type: journals
Aspirin attenuates the anti-inflammatory effects of theophylline via inhibition of cAMP production in mice with non-eosinophilic asthma.
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Theophylline is commonly used to treat severe asthma and chronic obstructive pulmonary disease (COPD) characterized by non-eosinophilic inflammation. Acetyl salicylic acid (ASA) is one of the most widely used medications worldwide, but up to 20% of patients with asthma experience aggravated respiratory symptoms after taking ASA. Here we evaluated the adverse effect of ASA on the therapeutic effect of theophylline in mice with non-eosinophilic asthma. A non-eosinophilic asthma mouse model was induced by airway sensitization with lipopolysaccharide (LPS)-containing allergen and then challenged with allergen alone. Therap...
Source: exp Mol Med - November 4, 2009 Category: Molecular Biology Authors: Moon HG, Kim YS, Choi JP, Choi DS, Yoon CM, Jeon SG, Gho YS, Kim YK Tags: Exp Mol Med Source Type: journals
Induction of TIMP-2 by cholesterol depletion leads to the conversion of pro MMP-2 into active-MMP-2 in human dermal fibroblasts.
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Cholesterol is one of major components of cell membrane and plays a role in vesicular trafficking and cellular signaling. We investigated the effects of cholesterol on MMP-2 activation in human dermal fibroblasts. We found that TIMP-2 expression and active form MMP-2 (64 kD) were dose-dependently increased by methyl-b-cyclodextrin (MbCD), a cholesterol depletion agent. In contrast, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation were suppressed by cholesterol repletion. Then we investigated the regulatory mechanism of TIMP-2 expression by cholesterol depletion. We found that the phosphorylation of ...
Source: exp Mol Med - November 4, 2009 Category: Molecular Biology Authors: Kim S, Oh JH, Lee Y, Lee J, Cho KH, Chung JH Tags: Exp Mol Med Source Type: journals
Neuronal RNA granule contains ApCPEB1, a novel Aplysia CPEB, in Aplysia sensory neuron.
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The cytoplasmic polyadenylation element (CPE)-binding protein (CPEB) binds to CPE containing mRNAs on their 3' untranslated regions (3'UTRs). This RNA binding protein comes out many important tasks, especially in learning and memory, by modifying the translational efficiency of target mRNAs via poly (A) tailing. Overexpressed CPEB has been reported to induce the formation of stress granules (SGs), a sort of RNA granule in mammalian cell lines. In these days, RNA granule is considered to be a potentially important factor in learning and memory. However, there is no study about RNA granule in Aplysia. To examine whether ...
Source: exp Mol Med - November 4, 2009 Category: Molecular Biology Authors: Chae YS, Lee SH, Cheang YH, Lee N, Rim YS, Jang DJ, Kaang BK Tags: Exp Mol Med Source Type: journals
Orphan nuclear receptor small heterodimer partner inhibits angiotensin II- stimulated PAI-1 expression in vascular smooth muscle cells.
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Angiotensin II is a major effector molecule in the development of cardiovascular disease. In vascular smooth muscle cells (VSMCs), angiotensin II promotes cellular proliferation and extracellular matrix accumulation through the upregulation of plasminogen activator inhibitor-1 (PAI-1) expression. Previously, we demonstrated that small heterodimer partner (SHP) represses PAI-1 expression in the liver through the inhibition of Transforming growth factor-b (TGF-b) signaling pathways. Here, we investigated whether SHP inhibited angiotensin II-stimulated PAI-1 expression in VSMCs. Adenovirus-mediated overexpression of SHP (...
Source: exp Mol Med - November 4, 2009 Category: Molecular Biology Authors: Lee KM, Seo HY, Kim MK, Min AK, Ryu SY, Kim YN, Park YJ, Choi HS, Lee KU, Park WJ, Park KG, Lee IK Tags: Exp Mol Med Source Type: journals
Mass spectrometry based cellular phosphoinositides profiling and phospholipid analysis: a brief review.
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Phospholipids are key components of cellular membrane and signaling. Among cellular phospholipids, phosphoinositides, phosphorylated derivatives of phosphatidylinositol are important as a participant in essential metabolic processes in animals. However, due to its low abundance in cells and tissues, it is difficult to identify the composition of phosphoinositides. Recent advances in mass spectrometric techniques, combined with established separation methods, have allowed the rapid and sensitive detection and quantification of a variety of lipid species including phosphoinositides. In this mini review, we briefly introd...
Source: exp Mol Med - November 4, 2009 Category: Molecular Biology Authors: Kim Y, Shanta SR, Zhou LH, Kim KP Tags: Exp Mol Med Source Type: journals
The function of p27(KIP1) during tumor development.
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Timely cell cycle regulation is conducted by sequential activation of a family of serine-threonine kinases called cycle dependent kinases (CDKs). Tight CDK regulation involves cyclin dependent kinase inhibitors (CKIs) which ensure the correct timing of CDK activation in different phases of the cell cycle. One CKI of importance is p27(KIP1). The regulation and cellular localization of p27(KIP1) can result in biologically contradicting roles when found in the nucleus or cytoplasm of both normal and tumor cells. The p27(KIP1) protein is mainly regulated by proteasomal degradation and its downregulation is often correlated...
Source: exp Mol Med - November 4, 2009 Category: Molecular Biology Authors: Lee J, Kim SS Tags: Exp Mol Med Source Type: journals
The Roles of Glycosphingolipids in the Proliferation and Neural Differentiation of Mouse Embryonic Stem Cells.
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In this study, Ugcg expression was reduced to approximately 80% by short hairpin RNAs (shRNAs) to evaluate the roles of GSLs in proliferation and neural differentiation of mouse embryonic stem cells (mESCs). HPTLC/immunofluorescence analyses of shRNA-transfected mESCs revealed that treatment with Ugcg-shRNA decreased expression of major gangliosides, GM3 and GD3. Furthermore, MTT and Western blot/immunofluorescence analyses demonstrated that inhibition of the Ugcg expression in mESCs resulted in decrease of cell proliferation (p <0.05) and decrease of activation of the ERK1/2 (p <0.05), respectively. To further inves...
Source: exp Mol Med - September 10, 2009 Category: Molecular Biology Authors: Jung JU, Lee DH, Ko K, Ko K, Choo YK Tags: Exp Mol Med Source Type: journals
Optimization of Streptomyces bacteriophage phiC31 integrase system to prevent post integrative gene silencing in pulmonary type II cells.
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phiC31 integrase has emerged as a potent tool for achieving long-term gene expression in different tissues. The present study aimed at optimizing elements of phiC31 integrase system for alveolar type II cells. Luciferase and beta galactosidase activities were measured at different time points post transfection. 5-Aza-2'deoxycytidine (AZA) and Trichostatin A (TSA) were used to inhibit DNA methyltransferase and histone deacetylase complex (HDAC) respectively. In A549 cells, expression of the integrase using a CMV promoter resulted in highest integrase activity, whereas in MLE12 cells, both CAG and CMV promoter were equal...
Source: exp Mol Med - September 10, 2009 Category: Molecular Biology Authors: Aneja MK, Geiger J, Imker R, Zg N S, Kormann M, Hasenpusch G, Maucksch C, Rudolph C Tags: Exp Mol Med Source Type: journals
LIN28B confer radio-resistance through the posttranscriptional control of KRAS.
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To screen the differentially expressed microRNAs related to radio-resistance, we compared the microRNA profiles of lung cancer cells with different responses to ionizing radiation (IR). Of 328 microRNAs in microarray, 27 microRNAs were differentially expressed in NCI-H460 (H460) and NCI-H1299 (H1299) cells. Among them, let-7g was down-regulated in radio-resistant H1299 cells, and the level of let-7g was higher in radio-sensitive cells like Caski, H460, and ME180 in qRT-PCR analysis than in radio-resistant cells like A549, H1299, DLD1, and HeLa. Over-expression of let-7g in H1299 cells could suppress the translation of ...
Source: exp Mol Med - September 10, 2009 Category: Molecular Biology Authors: Jeong SH, Wu HG, Park WY Tags: Exp Mol Med Source Type: journals
Fibroblasts in Three Dimensional Matrices: Cell Migration and Matrix Remodeling.
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Fibroblast-collagen matrix culture has facilitated the analysis of cell physiology under conditions that more closely resemble an in vivo-like environment compared to conventional 2-dimensional (2D) cell culture. Furthermore, it has led to significant progress in understanding reciprocal and adaptive interactions between fibroblasts and the collagen matrix, which occur in tissue. Recent studies on fibroblasts in 3-dimensional (3D) collagen matrices have revealed the importance of biomechanical conditions in addition to biochemical cues for cell signaling and migration. Depending on the surrounding mechanical conditions...
Source: exp Mol Med - September 10, 2009 Category: Molecular Biology Authors: Rhee S Tags: Exp Mol Med Source Type: journals
Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration.
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In this study, the expression of 4-1BB and 4-1BBL was examined during regeneration of the murine thymus following acute cyclophosphamide-induced involution. Four-color flow cytometry showed that 4-1BB and 4-1BBL were present in the normal thymus and were preferentially expressed in the regenerating thymus, mainly in CD4(+)CD8(+) double-positive (DP) thymocytes. Furthermore, the CD4(lo)CD8(lo), CD4(+)CD8(lo) and CD4(lo)CD8(+) thymocyte subsets, representing stages of thymocyte differentiation intermediate between DP and single-positive (SP) thymocytes, also expressed 4-1BB and 4-1BBL during thymus regeneration but to a less...
Source: exp Mol Med - September 10, 2009 Category: Molecular Biology Authors: Kim YM, Kim HK, Kim HJ, Lee HW, Ju SA, Choi BK, Kwon BS, Kim BS, Kim JB, Lim YT, Yoon S Tags: Exp Mol Med Source Type: journals
Activation of PPARgamma Induces Profound Multilocularization of Adipocytes in Adult Mouse White Adipose Tissues.
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We sought to determine the effects of activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on multilocularization of adipocytes in adult white adipose tissue (WAT). Male C57BL/6 normal, db/db, and ob/ob mice were treated with agonists of PPAR-gamma, PPAR-alpha, or beta(3)-adrenoceptor for 3 weeks. To distinguish multilocular adipocytes from unilocular adipocytes, whole-mounted adipose tissues were co-immunostained for perilipin and collagen IV. PPAR-gamma activation with rosiglitazone or pioglitazone induced a profound change of unilocular adipocytes into smaller, multilocular adipocytes in adult...
Source: exp Mol Med - September 10, 2009 Category: Molecular Biology Authors: Koh YJ, Park BH, Park JH, Han J, Lee IK, Park JW, Koh GY Tags: Exp Mol Med Source Type: journals
Cross-talk between BubR1 expression and commitment to differentiate in adipose-derived mesenchymal stem cells.
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In this study, we show that BubR1 depletion in human adipose-derived mesenchymal stem cells (ASCs) precedes the loss of differentiation potential and the induction of replicative senescence. These effects occur independently of p16(INK4A) expression and may involve DNA methylation. Our data therefore reveal a new and unsuspected feature of BubR1 expression in the regulation of adult stem cell differentiation.
PMID: 19745606 [PubMed - as supplied by publisher] (Source: exp Mol Med)
Source: exp Mol Med - September 10, 2009 Category: Molecular Biology Authors: Lee J, Lee CG, Lee KW, Lee CW Tags: Exp Mol Med Source Type: journals
The presence of CD8(+) invariant NKT cells in mice.
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Invariant natural killer T (iNKT) cells develop in the thymus upon recognition of CD1d expressed on developing thymocytes. Although CD4 and CD8 coreceptors are not directly involved in the interaction between CD1d and the TCRs of iNKT cells, a conspicuous lack of CD8(+) iNKT cells in mice raised the question of whether CD8(+) iNKT cells are excluded due to negative selection during their thymic development, or if there is no lineage commitment for the development of murine CD8(+) iNKT cells. To address this question, we analyzed iNKT cell-specific TCR Valpha14(+) transgenic mice, where the Valpha14 transgene forces the...
Source: exp Mol Med - September 10, 2009 Category: Molecular Biology Authors: Lee H, Hong C, Shin J, Oh S, Jung S, Park YK, Hong S, Lee GR, Park SH Tags: Exp Mol Med Source Type: journals
Nuclear Receptor Regulation of Stemness and Stem Cell Differentiation.
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Stem cells include a diverse number of toti-, pluri-, and multi-potent cells that play important roles in cellular genesis and differentiation, tissue development, and organogenesis. Genetic regulation involving various transcription factors results in the self-renewal and differentiation properties of stem cells. The nuclear receptor (NR) superfamily is composed of 48 ligand-activated transcription factors involved in diverse physiological functions such as metabolism, development, and reproduction. Increasing evidence shows that certain NRs function in regulating stemness or differentiation of embryonic stem (ES) cel...
Source: exp Mol Med - August 20, 2009 Category: Molecular Biology Authors: Jeong Y, Mangelsdorf DJ Tags: Exp Mol Med Source Type: journals
Analysis on genetic and non-genetic factors that determine QTc interval in Mongolian population: The GENDISCAN study.
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The QTc interval is a complex quantitative trait and a strong prognostic indicator of cardiovascular mortality in general healthy people. The aim of this study is to discover non-genetic factors and quantitative trait locus that govern the QTc interval in an isolated Mongolian population. We adopted multiple regression method to figure out the relation between the QTc interval and many non-genetic factors such as height, blood pressure and plasma lipid level. Whole genome linkage analyses were conducted to reveal quantitative trait locus of the QTc interval with 349 microsatellite (STR) markers from 1080 Mongolian. Amo...
Source: exp Mol Med - July 29, 2009 Category: Molecular Biology Authors: Im SW, Lee MK, Lee HJ, Oh SI, Kim HL, Sung J, Cho SI, Seo JS, Kim JI Tags: Exp Mol Med Source Type: journals
Characterization of mitosis-specific phosphorylation of tumor-associated microtubule-associated protein (TMAP).
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Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2), has been recently shown to be involved in the assembly and maintenance of mitotic spindle and also play an essential role in maintaining the fidelity of chromosome segregation during mitosis. We have previously reported that TMAP is phosphorylated at multiple residues specifically during mitosis, and characterized the mechanism and functional importance of phosphorylation at one of the mitosis-specific phosphorylation residues (i.e., Thr-622). However, the phosphorylation events at the remaining mitotic phos...
Source: exp Mol Med - July 29, 2009 Category: Molecular Biology Authors: Hong KU, Kim HJ, Bae CD, Park J Tags: Exp Mol Med Source Type: journals
Modulation of protective immunity against herpes simplex virus via mucosal genetic co-transfer of DNA vaccine with b2-adrenergic agonist.
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Cholera toxin, which has been frequently used as mucosal adjuvant, leads to an irreversible activation of adenylyl cyclase, thereby accumulating cAMP in target cells. Here, it was assumed that b2-adrenergic agonist salbutamol may have modulatory functions of immunity induced by DNA vaccine, since b2-adrenergic agonists induce a temporary cAMP accumulation. To test this assumption, the present study evaluated the modulatory functions of salbutamol co-administered with DNA vaccine expressing gB of herpes simplex virus (HSV) via intranasal (i.n.) route. We found that the i.n. co-administration of salbutamol enhanced gB-sp...
Source: exp Mol Med - July 29, 2009 Category: Molecular Biology Authors: Kim SB, Han YW, Rahman MM, Kim SJ, Yoo DJ, Kang SH, Kim K, Eo SK Tags: Exp Mol Med Source Type: journals
Possible Role of HMG CoA Reductase Inhibitor on Oxidative Stress Induced by Advanced Glycation Endproducts in Vascular Smooth Muscle Cells of Diabetic Vasculopathy.
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Conclusions Increased ROS formation, subsequent activation of mitogen-activated protein kinase (MAPK) system and increased VSMC proliferation may be possible mechanisms of diabetic vasculopathy induced by AGEs and statin may play a key role in the treatment of AGEs-induced diabetic atherosclerosis.
PMID: 19641377 [PubMed - as supplied by publisher] (Source: exp Mol Med)
Source: exp Mol Med - July 29, 2009 Category: Molecular Biology Authors: Yoon SJ, Yoon YW, Lee BK, Kwon HM, Hwang KC, Kim M, Chang W, Hong BK, Lee YH, Park SJ, Min PK, Rim SJ Tags: Exp Mol Med Source Type: journals
The Enabled Homolog Gene Polymorphisms as a Novel Susceptibility Gene for Childhood IgA Nephropathy.
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The enabled homolog gene (ENAH, hMena) is abundantly expressed in mesangial tissue, and might play an important role in inflammatory processes of IgA nephropathy (IgAN). The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the ENAH and childhood IgAN.We analyzed 12 SNPs of ENAH in 176 patients with childhood IgAN and 397 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to several clinical and pathological parameters. Genotyping data showed significant differences between IgAN patients and controls in the frequency of rs2...
Source: exp Mol Med - July 29, 2009 Category: Molecular Biology Authors: Hahn WH, Suh JS, Cho BS, Kim SD Tags: Exp Mol Med Source Type: journals
Effect of nicotinamide on early graft failure following intraportal islet transplantation.
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In this study, we tested the ability of nicotinamide to prevent early islet destruction in a syngeneic mouse model. Mice (C57BL/6) with chemically-induced diabetes received intraportal transplants of syngeneic islet tissue in various doses. Islets were cultured for 24 hr in medium with or without 10 mM NIC supplementation. Following IPIT, islet function was confirmed by an intraperitoneal glucose tolerance test (IPGTT) and hepatectomy. The effects of NIC were evaluated by blood glucose concentration, serum monocyte chemoattractant protein-1 (MCP-1) concentration, and immunohistology at 3 hr and 24 hr after IPIT. Among the ...
Source: exp Mol Med - July 29, 2009 Category: Molecular Biology Authors: Jung DY, Park JB, Joo SY, Joh JW, Kwon CH, Kwon GY, Kim SJ Tags: Exp Mol Med Source Type: journals
Candidate Gene Polymorphisms for Diabetes Mellitus, Cardiovascular Disease and Cancer are Associated with Longevity in Koreans.
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Long-lived people may have a unique genetic makeup that makes them more resistant than the general population to prevalent age-related diseases; however, not much is known about genes involved in the longevity. To identify susceptibility variants controlling longevity, we performed a high-throughput candidate gene study using 137 Koreans over 90 years old and 213 young healthy Koreans. We evaluated 463 informative markers located in 176 candidate genes mostly for diabetes mellitus, cardiovascular disease and cancer under five genetic models. We estimated the odds ratios for each allele, genotype, haplotype, and gene-ge...
Source: exp Mol Med - July 29, 2009 Category: Molecular Biology Authors: Park JW, Ji YI, Choi YH, Kang MY, Jung E, Cho SY, Cho HY, Kang BK, Joung YS, Kim DH, Park SC, Park J Tags: Exp Mol Med Source Type: journals
A reconstituted HDL containing V156K or R173C apoA-I exhibited anti-inflammatory activity in apo-E deficient mice and showed resistance to myeloperoxidase-mediated oxidation.
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In conclusion, blood infusions of the rHDLs exerted in vivo regression activity with anti-inflammatory and antioxidant activity in apo-E deficient mice and THP-1 cells, especially in those that were treated with V156K and R173C apoA-I.
PMID: 19322022 [PubMed - indexed for MEDLINE] (Source: exp Mol Med)
Source: exp Mol Med - June 29, 2009 Category: Molecular Biology Authors: Cho KH, Kim JR Tags: Exp Mol Med Source Type: journals
Sterol-independent repression of low density lipoprotein receptor promoter by peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1alpha).
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Peroxisome proliferator activated receptor (PPAR) gamma coactivator-1alpha (PGC-1alpha) may be implicated in cholesterol metabolism since PGC-1alpha co-activates estrogen receptor alpha (ERalpha) transactivity and estrogen/ERalpha induces the transcription of LDL receptor (LDLR). Here, we show that overexpression of PGC-1alpha in HepG2 cells represses the gene expression of LDLR and does not affect the ERalpha-induced LDLR expression. PGC-1alpha suppressed the LDLR promoter-luciferase (pLR1563- luc) activity regardless of cholesterol or functional sterol-regulatory element-1. Serial deletions of the LDLR promoter revea...
Source: exp Mol Med - June 29, 2009 Category: Molecular Biology Authors: Jeong JH, Cho S, Pak YK Tags: Exp Mol Med Source Type: journals
Involvement of betaPIX in angiotensin II-induced migration of vascular smooth muscle cells.
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Angiotensin II (Ang II) stimulates migration of vascular smooth muscle cell (VSMC) in addition to its contribution to contraction and hypertrophy. It is well established that Rho GTPases regulate cellular contractility and migration by reorganizing the actin cytoskeleton. Ang II activates Rac1 GTPase, but its upstream guanine nucleotide exchange factor (GEF) remains elusive. Here, we show that Ang II-induced VSMC migration occurs in a betaPIX GEF-dependent manner. betaPIX-specific siRNA treatment significantly inhibited Ang II-induced VSMC migration. Ang II activated the catalytic activity of betaPIX towards Rac1 in do...
Source: exp Mol Med - June 29, 2009 Category: Molecular Biology Authors: Shin EY, Lee CS, Park MH, Kim DJ, Kwak SJ, Kim EG Tags: Exp Mol Med Source Type: journals
Interleukin-1b promotes the expression of monocyte chemoattractant protein-1 (MCP1) in human aorta smooth muscle cells via multiple signaling pathways.
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In this study, we examined the intracellular signaling pathway of interleukin-1b (IL-1b)-induced MCP1 expression using various chemical inhibitors. The pretreatment of a phosphatidylcholine-specific phospholipase C (PC-PLC) inhibitor (D609), protein kinase C (PKC) inhibitors, or a nuclear factor-kB (NF-kB) inhibitor completely suppressed the IL-1b-induced MCP1 expression through blocking NF-kB translocation to the nucleus. Pretreatment with inhibitors of tyrosine kinase or phospholipase D (PLD) partially suppressed MCP1 expression and failed to block nuclear NF-kB translocation. These results suggest that IL-1b induces MCP...
Source: exp Mol Med - June 28, 2009 Category: Molecular Biology Authors: Lim JH, Um HJ, Park JW, Lee IK, Kwon TK Tags: Exp Mol Med Source Type: journals
Comparative Study of Synonymous Codon Usage Variations between the Nucleocapsid and Spike genes of Coronavirus, and C-type Lectin Domain Genes of Human and Mouse.
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In this study, we compared the synonymous codon usage patterns between the nucleocapsid and spike genes of CoVs, and C-type lectin domain (CTLD) genes of human and mouse on the codon basis. Findings indicate that the nucleocapsid genes of CoVs were affected from the synonymous codon usage bias than spike genes, and the CTLDs of human and mouse partially overlapped with the nucleocapsid genes of CoVs. In addition, we observed that CTLDs which showed the similar relative synonymous codon usage (RSCU) patterns with CoVs were commonly derived from the human chromosome 12, and mouse chromosome 6 and 12, suggesting that there mi...
Source: exp Mol Med - June 28, 2009 Category: Molecular Biology Authors: Ahn I, Jeong BJ, Son HS Tags: Exp Mol Med Source Type: journals
Alpha-tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells.
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Paclitaxel is one of the chemotheraputic drugs widely used for the treatment of nonsmall cell lung cancer (NSCLC) patients. Here, we tested the ability of alpha-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic doses of TOS greatly enhanced paclitaxel-induced growth suppression and apoptosis in the human H460 NSCLC cell lines. Our data revealed that this was accounted for primarily by an augmented cleavage of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8. Pretreatment with z-VAD-FMK (a pan-caspase inhi...
Source: exp Mol Med - June 28, 2009 Category: Molecular Biology Authors: Lim SJ, Choi MK, Kim MJ, Kim JK Tags: Exp Mol Med Source Type: journals
The adaptor protein, LAD/TSAd mediates Laminin-dependent T cell migration via association with the 67 kDa Laminin Binding Protein (LBP).
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The adaptor protein, LAD/TSAd, plays essential roles in T cell activation. To further understand the functions of this protein, we performed yeast two-hybrid screening using TSAd as bait and identified 67kDa Laminin Binding Protein (LBP) as the interacting partner. Subsequently, TSAd-LBP interaction was confirmed in D1.1 T cell line. Upon costimulation by TCR + laminin crosslinking or TCR + integrin alpha6 crosslinking, LBP was coimmunoprecipitated with TSAd. Moreover, TCR + laminin costimulation-dependent T cell migration was enhanced in D1.1 T cells overexpressing TSAd but was disrupted in D1.1 cells overexpressing d...
Source: exp Mol Med - June 28, 2009 Category: Molecular Biology Authors: Park E, Choi Y, Ahn E, Park I, Yun Y Tags: Exp Mol Med Source Type: journals
Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression.
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In this study, its ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of Triptolide on cancer progression. Treatment of mice with Triptolide decreased the incidence of colon cancer formation, and increased survival rate. Moreover, Triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, Triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK1,...
Source: exp Mol Med - June 28, 2009 Category: Molecular Biology Authors: Wang Z, Jin H, Xu R, Mei Q, Fan D Tags: Exp Mol Med Source Type: journals
Sequential Evolution of IL-17 Responses in the early period of allograft rejection.
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In conclusion, IL-17 is produced by neutrophils during the early postoperative period and subsequently by Th17 and CD8+ T cells during allograft rejection. Th17/Treg imbalance is associated with the development of allograft rejection. This study would provide basic information on Th17 biology for future investigation in the field of transplantation.
PMID: 19561402 [PubMed - as supplied by publisher] (Source: exp Mol Med)
Source: exp Mol Med - June 28, 2009 Category: Molecular Biology Authors: Min SI, Ha J, Park CG, Won JK, Park YJ, Min SK, Kim SJ Tags: Exp Mol Med Source Type: journals
Negative feedback regulation of Wnt signaling by Gbg-mediated reduction of Dishevelled.
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We report that guanine nucleotide binding protein beta 2 (Gnb2; Gb2) bound to Axin and Gb2 inhibited Wnt mediated reporter activity. The inhibition involved reduction of the level of Dvl, and the Gb2g2 mediated reduction of Dvl was countered by increased expression of Axin. Consistent with these effects in HEK293T cells, injection of Gb2g2 into Xenopus embryos inhibited the formation of secondary axes induced either by XWnt8 or Dvl, but not by b-catenin. The DEP domain of Dvl is necessary for both interaction with Gb2g2 and subsequent degradation of Dvl via the lysosomal pathway. Signaling induced by Gb2g2 is required beca...
Source: exp Mol Med - June 28, 2009 Category: Molecular Biology Authors: Jung H, Kim HJ, Lee SK, Kim R, Kopachik W, Han JK, Jho EH Tags: Exp Mol Med Source Type: journals
Legionella peptidoglycan-associated lipoprotein activates toll-like receptor 2 and induces cytokine production and expression of costimulatory molecules in peritoneal macrophages.
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In conclusions, these results indicate that Legionella PAL might activate macrophages via a TLR2-dependent mechanism which thus induce cytokine production and expression of costimulatory and MHC molecules.
PMID: 19561404 [PubMed - as supplied by publisher] (Source: exp Mol Med)
Source: exp Mol Med - June 28, 2009 Category: Molecular Biology Authors: Shim HK, Kim JY, Kim MJ, Sim HS, Park DW, Sohn JW, Kim MJ Tags: Exp Mol Med Source Type: journals
Triptolide-induced suppression of phospholipase D expression inhibits proliferation of MDA-MB-231 breast cancer cells.
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We examined one such here, denoted "Triptolide", which was identified in a chemical screen for inhibitors of PLD expression using cell assay system based on measurement of PLD promoter activity. Triptolide significantly suppressed the expression of both PLD1 and PLD2 with sub-mM potency in MDA-MB-231 breast cancer cells as analyzed by promoter assay and RT-PCR. Moreover, triptolide abolished the protein level of PLD in a time and dose-dependent manner. Triptolide-induced PLD1 downregulation was also observed in all the cancer cells examined, suggesting a general phenomenon detected in various cancer cells. Decrease of PLD ...
Source: exp Mol Med - May 28, 2009 Category: Molecular Biology Authors: Kang DW, Lee JY, Oh DH, Park SY, Woo TM, Kim MK, Park MH, Jang YH, Min DS Tags: Exp Mol Med Source Type: journals
SP600125 promotes the formation of polymerized tubulin, leading to G2/M phase arrest, endoreduplication, and delayed apoptosis.
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A c-Jun N-terminal kinase inhibitor, SP600125, strongly inhibits cell proliferation in many human cancer cells by blocking cell-cycle progression and inducing apoptosis. Despite extensive study, the mechanism by which SP600125 inhibits mitosis-related effects in human leukemia cells remains unclear. This present paper aims to investigate the effects of SP600125 on the inhibition of cell proliferation and the cell cycle and on microtubule (MT) dynamics in vivo and in vitro. Treatment of synchronized leukemia cells with varying concentrations of SP600125 has resulted in significant G2/M cell cycle arrest with elevated p2...
Source: exp Mol Med - May 28, 2009 Category: Molecular Biology Authors: Moon DO, Kim MO, Kang CH, Lee JD, Choi YH, Kim GY Tags: Exp Mol Med Source Type: journals
Curcumin inhibits cellular condensation and alters microfilament organization during chondrogenic differentiation of limb bud mesenchymal cells.
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Curcumin is well known a natural polyphenol product isolated from the rhizome of the plant Curcuma longa, anti-inflammatory agent for arthritis by inhibiting synthesis of inflammatory prostaglandins. However, the mechanisms by which curcumin regulates the functions of chondroprogenitor, such as proliferation, precartilage condensation, cytoskeletal organization or overall chondrogenic behavior, are largely unknown even though characteristic and actions of two cells, chondrogenic progenitor cells and articular chondrocytes. In the present report, we investigated the effects and signaling mechanism of curcumin on the reg...
Source: exp Mol Med - May 28, 2009 Category: Molecular Biology Authors: Kim DK, Kang SS, Kim SJ, Jin EJ Tags: Exp Mol Med Source Type: journals
Emodin Ameliorated High-glucose Induced Mesangial P38 Over-activation and Hypocontractility via Activating PPARgamma.
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In conclusion, emodin, possibly via activating PPARgamma, could effectively ameliorate high-glucose induced mesangial cells P38 over-activation and hypocontractility.
PMID: 19478555 [PubMed - as supplied by publisher] (Source: exp Mol Med)
Source: exp Mol Med - May 28, 2009 Category: Molecular Biology Authors: Liu Y, Jia L, Liu ZC, Zhang H, Zhang PJ, Wan Q, Wang R Tags: Exp Mol Med Source Type: journals
Comprehensive analysis of microRNA-mRNA co-expression in circadian rhythm.
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To investigate the potential role of microRNA (miRNA) in the regulation of circadian rhythm, we performed microarray-based expression profiling study of both miRNA and mRNA in mouse liver for 48 hours at 4-hour intervals. Circadian miRNA-mRNA target pair is defined as the pair both elements of which show circadian expression patterns and the sequence-based target relationship of which can be predicted. Circadian initiators, Clock and Bmal1, showed inversely correlated circadian expression patterns against their corresponding miRNAs, miR-181d and miR-191, targeting them. In contrast, circadian suppressors, Per, Cry, CKI...
Source: exp Mol Med - May 28, 2009 Category: Molecular Biology Authors: Na YJ, Sung JH, Lee SC, Lee YJ, Choi YJ, Park WY, Shin HS, Kim JH Tags: Exp Mol Med Source Type: journals
Differential regulation of inducible nitric oxide synthase and cyclooxygenase-2 expression by superoxide dismutase in lipopolysaccharide stimulated RAW 264.7 cells.
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This study was performed to determine the regulatory function of superoxide dismutase (SOD) on the LPS-induced expression of iNOS, and COX-2 in RAW 264.7 cells. When a cell-permeable SOD, Tat-SOD, was added to the culture medium of RAW 264.7 cells, it rapidly entered the cells in a dose-dependent manner. Treatment of RAW 264.7 cells with Tat-SOD led to decrease in LPS-induced ROS generation. Pretreatment with Tat-SOD significantly inhibited LPS-induced expression of iNOS and NO production but had no effect on the expression of COX-2 and PGE2 production in RAW 264.7 cells. Tat-SOD inhibited LPS-induced NF-kappaB DNA binding...
Source: exp Mol Med - May 28, 2009 Category: Molecular Biology Authors: Lee JA, Song HY, Ju SM, Lee SJ, Kwon HJ, Eum WS, Jang SH, Choi SY, Park J Tags: Exp Mol Med Source Type: journals
A Comprehensive Profile of DNA Copy Number Variations in a Korean Population: Identification of Copy Number Invariant Regions among Koreans.
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To examine copy number variations among the Korean population, we compared individual genomes with the Korean reference genome assembly using the publicly available Korean HapMap SNP 50K chip data from 90 individuals. Korean individuals exhibited 123 CNV regions (CNVRs) covering 27.2Mb, equivalent to 1.0% of the genome in the CNV analysis using the combined criteria of p value (p < 0.01) and standard deviation of copy numbers (SD >/= 0.25) among study subjects. In contrast, when compared to the Affymetrix reference genome assembly from multiple ethnic groups, considerably more CNVRs (n=643) were detected in large...
Source: exp Mol Med - May 28, 2009 Category: Molecular Biology Authors: Jeon JP, Shim SM, Jung J, Nam HY, Lee HJ, Oh B, Kimm K, Kim HL, Han BG Tags: Exp Mol Med Source Type: journals
Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1: implications for the pathogenesis of ALS.
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In this report we demonstrate that intracellular Abeta directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Abeta-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Abeta amino acids 26-42. Interestingly, intracellular Abeta binds to the SOD1 G93A mutant with greater affinity than to wild-type SOD1. This resulted in considerably less mutant enzymatic activity. Our study implicates a potential role for Abeta in the development of ALS by interacting with the SOD1 G93A mutant.
PMID: 19478559 [PubMed - as supplied by pu...
Source: exp Mol Med - May 28, 2009 Category: Molecular Biology Authors: Yoon EJ, Park HJ, Kim GY, Cho H, Choi JH, Park HY, Jang JY, Rhim H, Kang S Tags: Exp Mol Med Source Type: journals
Nickel induces secretion of IFN-gamma by splenic natural killer cells.
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Although nickel hypersensitivity is known as a delayed-type hypersensitivity mediated by nickel-specific T cells, it is greatly influenced by other immune cells. Here we show that splenic natural killer cells (NK cells) directly or indirectly respond to nickel by secretion of IFN-gamma. Using enzyme-linked immunosorbent spot (ELISPOT) assays, we found that nickel-reactive cells readily secreted IFN-gamma when splenocytes were cultured in the presence of varying concentrations of nickel sulfate (NiSO(4)) for 24 h. However, nickel-reactive IL-2- or IL- 4-secreting cells were infrequent during the 24-h culture with NiSO(4...
Source: exp Mol Med - April 29, 2009 Category: Molecular Biology Authors: Kim JY, Huh K, Lee KY, Yang JM, Kim TJ Tags: Exp Mol Med Source Type: journals
p47phox, the phagocyte NADPH oxidase/NOX2 organizer: structure, phosphorylation and implication in diseases.
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Phagocytes such as neutrophils play a vital role in host defense against microbial pathogens. The anti-microbial function of neutrophils is based on the production of superoxide anion (O2 -), which generates other microbicidal reactive oxygen species (ROS) and release of antimicrobial peptides and proteins. The enzyme responsible for O2 - production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two trans- membrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox a...
Source: exp Mol Med - April 29, 2009 Category: Molecular Biology Authors: El-Benna J, Dang PM, Gougerot-Pocidalo MA, Marie JC, Braut-Boucher F Tags: Exp Mol Med Source Type: journals
Neuronal activation increases the density of eukaryotic translation initiation factor 4E mRNA clusters in dendrites of cultured hippocampal neurons.
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In this study we show by fluorescence in situ hybridization (FISH) that the mRNA for eIF4E is present in the dendrites of cultured rat hippocampal neurons. Under basal culture conditions, 58.7+/-11.6% of the eIF4E mRNA clusters localize with or immediately adjacent to PSD-95 clusters. Neuronal activation with KCl (60 mM, 10 min) very significantly increases the number of eIF4E mRNA clusters in dendrites by 50.1 and 74.5% at 2 and 6 hr after treatment, respectively. In addition, the proportion of eIF4E mRNA clusters that localize with PSD-95 increases to 74.4+/-7.7% and 77.8+/-7.6% of the eIF4E clusters at 2 and 6 hr after ...
Source: exp Mol Med - April 20, 2009 Category: Molecular Biology Authors: Moon IS, Cho SJ, Seog DH, Walikonis R Tags: Exp Mol Med Source Type: journals
Stimulatory heterotrimeric G protein augments gamma ray-induced apoptosis by up-regulation of Bak expression via CREB and AP-1 in H1299 human lung cancer cells.
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This study aimed to investigate the effect of Gs? proteins on gamma ray-induced apoptosis of lung cancer cells and its molecular mechanism, as an attempt to develop a new strategy to improve the therapeutic efficacy of gamma radiation. Expression of constitutively active mutant of the a subunit of Gs (GasQL) augmented gamma ray-induced apoptosis via mitochondrial dependent pathway when assessed by clonogenic assay, FACS analysis of PI stained cells, and western blot analysis of the cytoplasmic translocation of cytochrome C and the cleavage of caspase-3 and PARP in H1299 human lung cancer cells. GasQL up-regulated the Bak e...
Source: exp Mol Med - April 20, 2009 Category: Molecular Biology Authors: Choi YJ, Kim SY, Oh JM, Juhnn YS Tags: Exp Mol Med Source Type: journals
Lysophosphatidylglycerol inhibits formyl peptide receptor like-1-stimulated chemotactic migration and IL-1b production from human phagocytes.
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In this study, we observed that lysophosphatidylglycerol (LPG) completely inhibited a formyl peptide receptor like-1 (FPRL1) agonist (MMK-1)-stimulated chemotactic migration in human phagocytes, such as neutrophils and monocytes. LPG also dramatically inhibited IL-1b production by another FPRL1 agonist serum amyloid A in human phagocytes. However, LPG itself induced intracellular calcium increase and superoxide anion production in human phagocytes. Keeping in mind that phagocytes migration and IL-1b production by FPRL1 are important for the induction of inflammatory response, our data suggest that LPG can be regarded as a ...
Source: exp Mol Med - April 20, 2009 Category: Molecular Biology Authors: Shim JW, Jo SH, Kim SD, Lee HY, Yun J, Bae YS Tags: Exp Mol Med Source Type: journals
Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis.
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During fasting periods, hepatic glucose production is enhanced by glucagon to provide fuels for other organs. This process is mediated via cAMP-dependent induction of the CREB Regulated Transcriptional Coactivator CRTC2, a critical transcriptional activator for hepatic gluconeogenesis. We have previously shown that CRTC2 activity is regulated by AMPK family members. Here we show that adiponectin and thiazolidinedione directly regulate AMPK to modulate CRTC2 activity in hepatocytes. Adiponectin or thiazolidinedione lowered glucose production from primary hepatocytes. Treatment of both reagents reduced gluconeogenic gene...
Source: exp Mol Med - April 20, 2009 Category: Molecular Biology Authors: Yoon YS, Ryu D, Lee MW, Hong S, Koo SH Tags: Exp Mol Med Source Type: journals
