Hepatocyte Nuclear Factor-4α Mediates Redox Sensitivity of Inducible Nitric Oxide Synthase Gene Transcription Running Title: HNF-4α, PC4 and Redox Regulation of iNOS Expression
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Hepatocyte nuclear factor-4α mediates redox sensitivity of inducible nitric-oxide synthase gene transcription.
The underlying redox-sensitive mechanisms that regulate hepatocyte expression of inducible nitric-oxide synthase (iNOS) and its antioxidant functions are largely unknown. We have demonstrated previously that oxidative stress induced by benzenetriol-mediated superoxide production increases interleukin-1beta-induced iNOS protein synthesis, steady state iNOS mRNA expression, NO production, iNOS ge...
متن کاملSerine/threonine phosphorylation regulates HNF-4alpha-dependent redox-mediated iNOS expression in hepatocytes.
Nitric oxide (NO), endogenously synthesized by inducible NO synthase (iNOS), serves antioxidant and antiapoptotic functions in settings characterized by oxidative stress and proinflammatory cytokines such as sepsis and shock. However, the redox-sensitive mechanisms regulating hepatocyte expression of iNOS are largely unknown. In interleukin-1beta (IL-1beta)-stimulated hepatocytes exposed to sup...
متن کاملSerine/threonine phosphorylation regulates HNF-4 -dependent redox-mediated iNOS expression in hepatocytes
Guo, Hongtao, Junping Wei, Yusuke Inoue, Frank J. Gonzalez, and Paul C. Kuo. Serine/threonine phosphorylation regulates HNF-4 -dependent redox-mediated iNOS expression in hepatocytes. Am J Physiol Cell Physiol 284: C1090–C1099, 2003. First published December 4, 2002; 10.1152/ajpcell.00394.2002.—Nitric oxide (NO), endogenously synthesized by inducible NO synthase (iNOS), serves antioxidant and a...
متن کاملPhosphorylation of Ser158 regulates inflammatory redox-dependent hepatocyte nuclear factor-4α transcriptional activity
In IL-1β (interleukin 1β)-stimulated rat hepatocytes exposed to superoxide, we have previously identified an IRX (inflammatory redox)-sensitive DR1 [direct repeat of RG(G/T)TCA with one base spacing] cis-acting activator element (nt –1327 to –1315) in the iNOS (inducible nitric oxide synthase) promoter: AGGTCAGGGGACA. The corresponding transcription factor was identified to be HNF4α (hepatocyte...
متن کاملIdentification of HNF-4α as a key transcription factor to promote ChREBP expression in response to glucose.
Transcription factor carbohydrate responsive element binding protein (ChREBP) promotes glycolysis and lipogenesis in metabolic tissues and cancer cells. ChREBP-α and ChREBP-β, two isoforms of ChREBP transcribed from different promoters, are both transcriptionally induced by glucose. However, the mechanism by which glucose increases ChREBP mRNA levels remains unclear. Here we report that hepatoc...
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