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Transcription Factor Activation (transcription + factor_activation)
Selected AbstractsActivation Of Mitogen Activated Protein Kinases (Mapks) In Response To High Glucose In Primary Sensory NeuronesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000T Purves In diabetes high glucose stresses cells as a prelude to complications. The MAPKs are serine-threonine kinases, which are putative glucose stress transducers, comprising extracellular signal regulated kinases (ERKs), p38 and c-Jun, n-terminal kinases (JNKs). In 10 week streptozotocin-induced diabetic rats JNK activation was increased when compared to age matched controls. This study aimed to determine the signaling pathways activated in response to high glucose in adult sensory neurones in vitro. Cultures of adult rat dorsal root ganglia (DRG) were treated with 10mM, 25mM and 50mM glucose for 16 hours. MAPK activation was examined in Western blots using antibodies raised against phosphorylated and non-phosphorylated epitopes (results expressed as a ratio of phosphorylated to non-phosphorylated kinase). Glucose caused a concentration-dependent increase in phospho-p38 with a 1.6 fold increase at 25mM (0.77 ± 1.04) and a 2.4 fold increase at 50mM (1.18 ± 1.44) when compared to 10mM (0.49 ± 0.60) glucose. Phosphorylation of the p56 JNK isoform increased 2.4 fold (4.37 ± 3.59) and the p46 isoform 2.2 fold (1.95 ± 1.35) at 50mM glucose when compared to 10mM (p56 1.80 ± 0.99, p46 0.88 ± 0.31). ERK phosphorylation remained unchanged in 3 different experiments. Immunocytochemistry located these changes to neurones, rather than the small percentage of non-neurones that remain in culture. Transcription factor activation as a result of MAPK activation is being investigated using electrophoretic mobility shift assays. We conclude that the activation of MAPK pathways is involved in the response of neuronal cells to high glucose stress. [source] Misregulation of gene expression in the redox-sensitive NF-,b-dependent limb outgrowth pathway by thalidomideDEVELOPMENTAL DYNAMICS, Issue 2 2002Jason M. Hansen Abstract Thalidomide is known to induce oxidative stress, but mechanisms have not been described through which oxidative stress could contribute to thalidomide-induced terata. Oxidative stress modulates intracellular glutathione (GSH) and redox status and can perturb redox-sensitive processes, such as transcription factor activation and/or binding. Nuclear factor-kappa B (NF-,B), a redox-sensitive transcription factor involved in limb outgrowth, may be modulated by thalidomide-induced redox shifts. Thalidomide-resistant Sprague-Dawley rat embryos (gestation day [GD] 13) treated with thalidomide in utero showed no changes in GSH distribution in the limb but thalidomide-sensitive New Zealand White rabbit embryos (GD 12) showed selective GSH depletion in the limb bud progress zone (PZ). NF-,B and regulatory genes that initiate and maintain limb outgrowth and development, such as Twist and Fgf-10, are selectively expressed in the PZ. Green fluorescent protein (GFP) reporter vectors containing NF-,B binding promoter sites were transfected into both rat and rabbit limb bud cells (LBCs). Treatment with thalidomide caused a preferential decrease in GFP expression in rabbit LBCs but not in rat LBCs. N-acetylcysteine and ,-N-t-phenylbutyl nitrone (PBN), a free radical trapping agent, rescued GFP expression in thalidomide-treated cultures compared with cultures that received thalidomide only. In situ hybridization showed a preferential decrease in Twist, Fgf-8, and Fgf-10 expression after thalidomide treatment (400 mg/kg per day) in rabbit embryos. Expression in rat embryos was not affected. Intravenous cotreatment with PBN and thalidomide (gavage) in rabbits restored normal patterns and localization of Twist, Fgf-8, and Fgf-10 expression. These findings show that NF-,B binding is diminished due to selective thalidomide-induced redox changes in the rabbit, resulting in the significant attenuation of expression of genes necessary for limb outgrowth. © 2002 Wiley-Liss, Inc. [source] Aberrant signalling and transcription factor activation as an explanation for the defective growth control and differentiation of keratinocytes in psoriasis: a hypothesisEXPERIMENTAL DERMATOLOGY, Issue 4 2003R. C. McKenzie Abstract:, Psoriasis is a chronic inflammatory skin disease characterized by the accumulation of red, scaly plaques on the skin. The plaques result from hyperproliferation and incomplete differentiation of keratinocytes (KC) in a process that seems to be driven, in part by skin-infiltrating leucocytes. We believe that the KC have inherent defects in intracellular signalling which could be usefully targeted to allow the development of more effective therapies. We suggest that there are defects in the regulation of the transcription factors: signal transducer and activator of transcription (STAT-1,), interferon regulated factor-1 (IRF-1) and NF,B which lead to loss of growth and differentiation control when the cells are subjected to physico-chemical and immunological stress. We also highlight recent studies that suggest that peroxisome proliferator-activated receptors, the notch receptor and defects in calcium and other ion transporting proteins may contribute to impairment in the ability of psoriatic KC to differentiate. The role of these systems in the development of the psoriatic phenotype and tests of these hypotheses are proposed. [source] Alcoholic fatty liver differentially induces a neutrophil-chemokine and hepatic necrosis after ischemia-reperfusion in ratHEPATOLOGY, Issue 2 2000Shinwa Yamada M.D. Primary graft nonfunction of steatotic liver allograft is one of the factors causing shortage of donor livers. Ischemia/reperfusion (I/R) injury is an important contributory factor to primary graft nonfunction. In this study, we investigated the complex chain of events from transcription factor activation to necrosis through cytokine induction and apoptosis in steatotic rat liver after warm I/R. Rats with alcoholic or nonalcoholic fatty liver were subjected to hepatic warm I/R and compared with control rats. Rats fed an ethanol diet for 6 to 8 weeks developed severe hepatic necrosis accompanied by increased neutrophil recruitment after I/R, compared with rats with nonalcoholic fatty liver or control. Hepatic apoptosis as assessed by DNA fragmentation at 4 hours after I/R, however, increased to a similar degree in each of the 2 fatty liver models compared with the control. Alcoholic fatty liver exposed to I/R showed a rapid increase in nuclear factor-,B (NF-,B) binding activity at 1 hour after I/R, which preceded an increased expression of tumor necrosis factor , (TNF-,) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In contrast, nonalcoholic fatty liver did not show such potentiation of either NF-,B activation or cytokine induction after I/R. Our results have indicated that alcoholic fatty liver may differentially induce CINC-1 production and hepatic necrosis after I/R. Furthermore, our results suggest that apoptosis per se does not always lead to necrosis in the liver following I/R. [source] Nucleosomes activate NF-,B in endothelial cells for induction of the proangiogenic cytokine IL-8INTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Jerome E. Tanner Abstract Solid tumors often exhibit regions undergoing apoptosis and necrosis, also referred to as "aponecrosis", juxtaposed to sites of active angiogenesis. We explored whether nucleosomes resulting from aponecrosis induced the angiogenic factor IL-8 in vascular endothelial cells. Results indicate that nucleosomes induced IL-8. Nucleosomes increased IL-6 and IL-8 mRNA but not IL-10, TNF-,, VEGF or FGF-2 mRNA. Induction of IL-8 by nucleosomes in endothelial cells appeared to be the result of NF-,B/RelA transcription factor activation. The increased expression of IL-8 in vascular endothelial cells following nucleosome stimulation suggests that aponecrosis could play an important role in the promotion of tumor angiogenesis. © 2004 Wiley-Liss, Inc. [source] Hypoxia-inducible factor and nuclear factor kappa-B activation in blood,brain barrier endothelium under hypoxic/reoxygenation stressJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Ken A. Witt Abstract This investigation focuses on transcription factor involvement in blood,brain barrier (BBB) endothelial cell-induced alterations under conditions of hypoxia and post-hypoxia/reoxygenation (H/R), using established in vivo/ex vivo and in vitro BBB models. Protein/DNA array analyses revealed a correlation in key transcription factor activation during hypoxia and H/R, including NF,B and hypoxia-inducible factor (HIF)1. Electrophoretic mobility shift assays confirmed NF,B and HIF1 binding activity ex vivo and in vitro, under conditions of hypoxia and H/R. Hypoxia- and H/R-treated BBB endothelium showed increased HIF1, protein expression in both cytoplasmic and nuclear fractions, in ex vivo and in vitro models. Co-immunoprecipitation of HIF1, and HIF1, was shown in the nuclear fraction under conditions of hypoxia and H/R in both models. Hypoxia- and H/R-treated BBB endothelium showed increased expression of NF,B-p65 protein in both cytoplasmic and nuclear fractions. Co-immunoprecipitation of NF,B-p65 with NF,B-p50 was shown in the nuclear fraction under conditions of hypoxia and H/R in the ex vivo model, and after H/R in the in vitro model. These data offer novel avenues in which to alter and/or investigate BBB activity across model systems and to further our understanding of upstream regulators during hypoxia and H/R. [source] | |||||||||||||