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Nuclear Transcription Factors (nuclear + transcription_factor)
Selected AbstractsCardiovascular effects of the thiazolidinedionesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2006Rehan Qayyum Abstract Thiazolidinediones, used for the treatment of diabetes mellitus type 2, modulate gene expression by binding to nuclear transcription factor, peroxisome proliferator-activated receptor-gamma. Peroxisome proliferator,activated receptor-gamma is expressed in several tissues, therefore, thiazolidinediones have biological effects on multiple organ systems. Here, we describe evidence that thiazolidinediones have beneficial effects on the cardiovascular system independent of their antidiabetic effect. Studies in animals have clearly shown that thiazolidinediones decrease blood pressure, left ventricular hypertrophy, development of atherosclerotic lesions, and protect myocardium from ischemia/reperfusion injury. Although relatively few studies in humans have been reported, the preponderance of available evidence suggests a beneficial effect of thiazolidinediones. Thus, by modulating gene expression, thiazolidinediones may provide a novel method for the prevention and treatment of cardiovascular diseases. Copyright © 2005 John Wiley & Sons, Ltd. [source] Chronic ethanol increases adeno-associated viral transgene expression in rat liver via oxidant and NF,B-dependent mechanismsHEPATOLOGY, Issue 5 2000Michael D. Wheeler Recombinant adeno-associated virus (rAAV) transduction is limited in vivo, yet can be enhanced by hydroxyurea, ultraviolet-irradiation, or adenovirus coinfection, possibly via mechanisms involving stress in the host cell. Because chronic ethanol induces oxidative stress, it was hypothesized that chronic ethanol would increase rAAV transduction in vivo. To test this hypothesis, rAAV encoding ,-galactosidase was given to Wistar rats that later received either ethanol diet or high-fat control diet via an enteral-feeding protocol for 3 weeks. Expression and activity of ,-galactosidase in the liver were increased nearly 5-fold by ethanol. The increase in transgene expression was inhibited by antioxidant diphenylene iodonium (DPI), which is consistent with the hypothesis that ethanol causes an increase in rAAV transduction via oxidative stress. Ethanol increased DNA synthesis only slightly; however, it increased the nuclear transcription factor ,B (NF,B) 4-fold, a phenomenon also sensitive to DPI. Moreover, a 6-fold increase in rAAV transgene expression was observed in an acute ischemia-reperfusion model of oxidative stress. Transgene expression was transiently increased 24 hours after ischemia-reperfusion 3 days and 3 weeks after rAAV infection. Further, adenoviral expression of superoxide dismutase or I,B, superrepressor inhibited rAAV transgene expression caused by ischemia-reperfusion. Therefore, it is concluded that ethanol increases rAAV transgene expression via mechanisms dependent on oxidative stress, and NF,B likely through enhancement of cytomegaloviral (CMV) promoter elements. Alcoholic liver disease is an attractive target for gene therapy because consumption of ethanol could theoretically increase expression of therapeutic genes (e.g., superoxide dismutase). Moreover, this study has important implications for rAAV gene therapy and potential enhancement and regulation of transgene expression in liver. [source] The moleskin gene product is essential for Caudal-mediated constitutive antifungal Drosomycin gene expression in Drosophila epitheliaINSECT MOLECULAR BIOLOGY, Issue 3 2004S.-H. Han Abstract The homeobox gene, Caudal, encodes the DNA-binding nuclear transcription factor that plays a crucial role during development and innate immune response. The Drosophila homologue of importin-7 (DIM-7), encoded by moleskin, was identified as a Caudal-interacting molecule during yeast two-hybrid screening. Both mutation of the minimal region of Caudal responsible for moleskin binding and RNA interference (RNAi) of moleskin dramatically inhibited the Caudal nuclear localization. Furthermore, Caudal-mediated constitutive expression of antifungal Drosomycin gene was severely affected in the moleskin- RNAi flies, showing a local Drosomycin expression pattern indistinguishable from that of the Caudal- RNAi flies. These in vivo data suggest that DIM-7 mediates Caudal nuclear localization, which is important for the proper Caudal function necessary for regulating innate immune genes in Drosophila. [source] Role of the Bone Marrow Microenvironment in Multiple Myeloma,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2002G. David Roodman M.D., Ph.D. Abstract On June 26,27, 2001, the Sixth Research Roundtable in Multiple Myeloma, entitled "The Role of the Bone Microenvironment in Multiple Myeloma," was held and focused on the biology of cell-to-cell interactions, the mediators of bone disease, and novel treatment strategies for myeloma. Studies on cell-cell interactions showed that vascular cell adhesion molecule 1, expressed by local endothelial and stromal cells, binds to tumor cell surface integrins in which expression may be increased by tumor cell-derived chemokines such as macrophage inflammatory protein (MIP) 1,. These adhesive interactions increase production and release of vascular endothelial growth factor (VEGF). Studies on myeloma bone disease showed the ligand for receptor activator of nuclear transcription factor-,B (RANKL) was expressed on tumor cells and stromal cells associated with myeloma cells and was critical for osteoclast-induced osteolysis. Blockade of RANKL suppressed osteoclast maturation, bone resorption, and tumor development. Bisphosphonates, in addition to reducing osteoclast mobility and inducing osteoclast apoptosis, also decreased tumor cell adhesion to stroma. Immunomodulatory drugs such as thalidomide analogues targeted these tumor cell-stromal cell interactions, blocking both secretion of cytokines and activation of intracellular signaling pathways required for tumor survival and growth. These agents induced tumor cell apoptosis, decreased neovascularization, and potentiated natural killer cell activity. The proteasome inhibitor PS-341 also prevented expression of adhesion molecules and cytokines and triggered tumor cell apoptosis, even in drug-resistant cell lines, while showing minimal activity in healthy cells. In addition, potential therapeutic agents under investigation, which included RANKL antagonists, protein prenylation inhibitors, and osteoblast growth factors, were discussed. [source] Matrine inhibits PMA-induced MMP-1 expression in human dermal fibroblastsBIOFACTORS, Issue 2 2008Eunsun Jung Abstract Matrix metalloproteinase-1 (MMP-1) plays an important role in the maintenance and turnover of extracellular matrix (ECM) macromolecules. Remodelling of extracellular matrix by MMPs is a hallmark feature of physiological and pathological processes. In this study, in order to establish the therapeutic potential of matrine, we investigated its effect on MMP-1 expression in human dermal fibroblast cells. We found that matrine inhibited both MMP-1 mRNA and protein expression induced by PMA (phorbol myristate acetate). Therefore, we characterized the inhibitory mechanism of matrine on PMA-induced MMP-1 expression. Matrine inhibited PMA-induced activation of the AP-1 promoter, an important nuclear transcription factor in MMP-1 expression. Additionally, we detected that matrine suppressed the PMA-induced phosphorylation of two mitogen-activated protein kinases, extracellular signal-regulated protein kinase and c-Jun N-terminal kinase, but did not suppress the PMA-induced phosphorylation of p38 kinase. These results suggest that matrine suppresses PMA-induced MMP-1 expression through inhibition of the AP-1 signaling pathway and also may be beneficial for treatment of some inflammatory skin disorders. [source] Increase in nuclear translocation of nuclear transcription factor-,B following infection of a human Schwann cell line with Leishmania amazonensisBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2008W. Baetas-Da-Cruz No abstract is available for this article. [source] Overview of retinoid metabolism and functionDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2006Rune Blomhoff Abstract Retinoids (vitamin A) are crucial for most forms of life. In chordates, they have important roles in the developing nervous system and notochord and many other embryonic structures, as well as in maintenance of epithelial surfaces, immune competence, and reproduction. The ability of all- trans retinoic acid to regulate expression of several hundred genes through binding to nuclear transcription factors is believed to mediate most of these functions. The role of all- trans retinoic may extend beyond the regulation of gene transcription because a large number of noncoding RNAs also are regulated by retinoic acid. Additionally, extra-nuclear mechanisms of action of retinoids are also being identified. In organisms ranging from prokaryotes to humans, retinal is covalently linked to G protein-coupled transmembrane receptors called opsins. These receptors function as light-driven ion pumps, mediators of phototaxis, or photosensory pigments. In vertebrates phototransduction is initiated by a photochemical reaction where opsin-bound 11- cis -retinal is isomerized to all- trans -retinal. The photosensitive receptor is restored via the retinoid visual cycle. Multiple genes encoding components of this cycle have been identified and linked to many human retinal diseases. Central aspects of vitamin A absorption, enzymatic oxidation of all- trans retinol to all- trans retinal and all- trans retinoic acid, and esterification of all- trans retinol have been clarified. Furthermore, specific binding proteins are involved in several of these enzymatic processes as well as in delivery of all- trans retinoic acid to nuclear receptors. Thus, substantial progress has been made in our understanding of retinoid metabolism and function. This insight has improved our view of retinoids as critical molecules in vision, normal embryonic development, and in control of cellular growth, differentiation, and death throughout life. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 606,630, 2006 [source] Peroxisome proliferator-activated receptors (PPARs) in the control of bone metabolismFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2007Costas Giaginis Abstract Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that regulate the storage and catabolism of dietary fats. PPARs constitute molecular targets for the treatment of human metabolic disorders, and also play a crucial role in inflammatory-related disease and cancer. Recent evidence has revealed the presence of three different PPAR isotypes (,, ,/,, and ,) in different cells of the bone tissue, as well as the possible role of PPAR ligands in bone turnover. In the present review, the latest knowledge of the expression of PPARs in bone tissue and the diverse effects of PPAR ligands on bone metabolism is summarized. PPARs, especially of the , isotype, could be targets for the treatment of diverse bone diseases such as osteoporosis and osteopenia related to either diabetes or aging. [source] Steroid and thyroid hormone receptors in mitochondriaIUBMB LIFE, Issue 4 2008Anna-Maria G. Psarra Abstract Receptors for glucocorticoids, estrogens, androgens, and thyroid hormones have been detected in mitochondria of various cell types by Western blotting, immunofluorescence labeling, confocal microscopy, and immunogold electron microscopy. A role of these receptors in mitochondrial transcription, OXPHOS biosynthesis, and apoptosis is now being revealed. Steroid and thyroid hormones regulate energy production, inducing nuclear and mitochondrial OXPHOS genes by way of cognate receptors. In addition to the action of the nuclearly localized receptors on nuclear OXPHOS gene transcription, a parallel direct action of the mitochondrially localized receptors on mitochondrial transcription has been demonstrated. The coordination of transcription activation in nuclei and mitochondria by the respective receptors is in part realized by their binding to common trans acting elements in the two genomes. Recent evidence points to a role of the mitochondrial receptors in cell survival and apoptosis, exerted by genomic and nongenomic mechanisms. The identification of additional receptors of the superfamily of nuclear receptors and of other nuclear transcription factors in mitochondria increases their arsenal of regulatory molecules and further underlines the central role of these organelles in the integration of growth, metabolic, and cell survival signals. © 2008 IUBMB IUBMB Life, 60(4): 210,223, 2008 [source] TCDD suppresses insulin-responsive glucose transporter (GLUT-4) gene expression through C/EBP nuclear transcription factors in 3T3-L1 adipocytesJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2006Phillip Chin-Chen Liu Abstract TCDD is known to reduce significantly the level of the functionally active form of glucose transporter type 4 (GLUT4) in vivo in adipose tissue and muscles. To study the mechanistic basis of this phenomenon, we conducted transient transfection and DNA deletion analysis in 3T3-L1 cells using chloramphenicol acetyltransferase (CAT) reporter plasmids containing the GLUT4 promoter joined to the bacterial CAT. It was found that in transfected control samples, CAT activity was significantly higher in cells transfected with p469CAT and p273CAT than those with p78CAT, indicating that the region between ,78 and ,273 contained elements that play major roles in transactivation of this gene. Treatment with TCDD decreased CAT activity with p469CAT and p273CAT, but not with p78CAT, indicating the same region to contain the element(s) affected by TCDD. A gel-shift (EMSA) analysis result indicated that TCDD shows the profound effect only on the nuclear proteins binding to the [32P]-labeled probe containing C/EBP response element equivalent of the ,265 to ,242 stretch of the GLUT4 promoter. The results of supershift analysis showed that TCDD caused a decrease in the tier of C/EBP, and an increase in that of C/EBP, among the proteins bound to this C/EBP response element. We studied the effect of TCDD in cells overexpressing either C/EBP,, C/EBP,, or C/EBP, through transient transfection of p273CAT or p469CAT. The results clearly showed that the effect of TCDD to suppress the CAT activity of p273 or p469 disappeared in those cells overexpressing C/EBP, or C/EBP,. These results implicate the C/EBP proteins to be the main mediator of suppressive action of TCDD on GLUT4 gene expression in 3T3-L1 cells. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:79,87, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20120 [source] Astaxanthin protects mesangial cells from hyperglycemia-induced oxidative signaling,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2008Emiko Manabe Abstract Astaxanthin (ASX) is a carotenoid that has potent protective effects on diabetic nephropathy in mice model of type 2 diabetes. In this study, we investigated the protective mechanism of ASX on the progression of diabetic nephropathy using an in vitro model of hyperglycemia, focusing on mesangial cells. Normal human mesangial cells (NHMCs) were cultured in the medium containing normal (5 mM) or high (25 mM) concentrations of D -glucose. Reactive oxygen species (ROS) production, the activation of nuclear transcription factors such as nuclear factor kappa B (NF,B) and activator protein-1 (AP-1), and the expression/production of transforming growth factor-beta 1 (TGF,1) and monocyte chemoattractant protein-1 (MCP-1) were evaluated in the presence or absence of ASX. High glucose (HG) exposure induced significant ROS production in mitochondria of NHMCs, which resulted in the activation of transcription factors, and subsequent expression/production of cytokines that plays an important role in the mesangial expansion, an important event in the pathogenesis of diabetic nephropathy. ASX significantly suppressed HG-induced ROS production, the activation of transcription factors, and cytokine expression/production by NHMCs. In addition, ASX accumulated in the mitochondria of NHMCs and reduced the production of ROS-modified proteins in mitochondria. ASX may prevent the progression of diabetic nephropathy mainly through ROS scavenging effect in mitochondria of mesangial cells and thus is expected to be very useful for the prevention of diabetic nephropathy. J. Cell. Biochem. 103: 1925,1937, 2007. © 2007 Wiley-Liss, Inc. [source] Inositol hexaphosphate inhibits ultraviolet B,induced signal transductionMOLECULAR CARCINOGENESIS, Issue 3 2001Nanyue Chen Abstract Inositol hexaphosphate (InsP6) has an effective anticancer action in many experimental models in vivo and in vitro. Ultraviolet B (UVB) radiation is believed to be responsible for many of the carcinogenic effects related to sun exposure, and alteration in UVB-induced signal transduction is associated with UVB-induced carcinogenesis. Here we report the effects of InsP6 on UVB-induced signal transduction. InsP6 strongly blocked UVB-induced activator protein-1 (AP-1) and NF-,B transcriptional activities in a dose-dependent manner. InsP6 also suppressed UVB-induced AP-1 and nuclear factor ,B (NF-,B) DNA binding activities and inhibited UVB-induced phosphorylation of extracellular signal-regulated protein kinases (Erks) and c-Jun NH2-terminal kinases (JNKs). Phosphorylation of p38 kinases was not affected. InsP6 also blocked UVB-induced phosphorylation of I,B-,, which is known to result in the inhibition of NF-,B transcriptional activity. InsP6 does not block UVB-induced phosphotidylinositol-3, (PI-3) kinase activity, suggesting that the inhibition of UVB-induced AP-1 and NF-,B activities by InsP6 is not mediated through PI-3 kinase. Because AP-1 and NF-,B are important nuclear transcription factors that are related to tumor promotion, our work suggests that InsP6 prevents UVB-induced carcinogenesis by inhibiting AP-1 and NF-,B transcription activities. © 2001 Wiley-Liss, Inc. [source] Enteric nervous system disorders: genetic and molecular insights for the neurogastroenterologistNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2001M. Camilleri The goals of this review are to summarize some of the novel observations on the genetic and molecular basis of enteric nervous system disorders, with particular emphasis on the relevance of these observations to the practicising neurogastroenterologist. In the last two decades, there has been a greater understanding of genetic loci involved in congenital forms of pseudo-obstruction and Hirschsprung's disease; and the contribution of endothelins and nuclear transcription factors to the development of the enteric nervous system. In addition, clarification of the molecules involved in the activation of the peristaltic reflex, the disorders of the interstitial cells of Cajal, the clinical manifestations of mitochondrial cytopathies affecting the gut, and the application of neurotrophic factors for disorders of colonic function have impacted on practical management of patients with gut dysmotility. [source] Oxidoreductase macrophage migration inhibitory factor is simultaneously increased in leukocyte subsets of patients with severe sepsisBIOFACTORS, Issue 4 2008Lutz E. Lehmann M.D. Abstract The oxidoreductase Macrophage Migration Inhibitory Factor (MIF) is discussed as a promising target for immunomodulatory therapy in patients with severe sepsis. Moreover, MIF expresses tautomerase as well as thiol-protein oxidore-ductase activities and has a potential role in cellular redox homeostasis, apoptosis inhibition, endotoxin responsiveness as well as regulation of nuclear transcription factors. To further elucidate a potential role of intracellular MIF in severe sepsis, we assessed alterations of intracellular MIF content in peripheral blood leukocytes of patients with severe sepsis in comparison to healthy controls and non-septic patients after major surgery. Intracellular MIF was significantly elevated simultaneously in lymphocytes, B-cells, macrophages and granulocytes of patients with severe sepsis when compared to healthy control individuals (p < 0.05) and increased when compared to non-septic patients after major surgery. In parallel, plasma MIF levels were elevated in severe sepsis (p < 0.05). There was no difference of intracellular MIF in lymphocytes, B-cells, macrophages or granulocytes between surviving and non-surviving patients with severe sepsis (p > 0.05). However, in survivors LPS ex vivo stimulation increased MIF secretion but not in non-survivors of sepsis (p < 0.05). This finding underlines the role of intracellular MIF in inflammatory diseases. It suggests monitoring of intracellular MIF in further clinical and non-clinical research valuable. [source] Bisphenol A diglycidyl ether (BADGE) is a PPAR, agonist in an ECV304 cell lineBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000David Bishop-Bailey Peroxisome proliferator activated receptors (PPAR)s are nuclear transcription factors of the steroid receptor super-family. One member, PPAR,, a critical transcription factor in adipogenesis, is expressed in ECV304 cells, and when activated participates in the induction of cell death by apoptosis. Here we describe a clone of ECV304 cells, ECV-ACO.Luc, which stably expresses a reporter gene for PPAR activation. ECV-ACO.Luc respond to the PPAR, agonists, 15-deoxy-,12,14 PGJ2, and ciglitizone, by inducing luciferase expression. Furthermore, using ECV-ACO.Luc, we demonstrate that a newly described PPAR, antagonist, bisphenol A diglycidyl ether (BADGE) has agonist activities. Similar to 15-deoxy-,12,14 PGJ2, BADGE induces PPAR, activation, nuclear localization of the receptor, and induces cell death. British Journal of Pharmacology (2000) 131, 651,654; doi:10.1038/sj.bjp.0703628 [source] | |||||||||||||