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Serine/threonine phosphorylation regulates HNF-4alpha-dependent redox-mediated iNOS expression in hepatocytes.

Publication ,  Journal Article
Guo, H; Wei, J; Inoue, Y; Gonzalez, FJ; Kuo, PC
Published in: Am J Physiol Cell Physiol
April 2003

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 superoxide, we demonstrate that hepatocyte nuclear factor-4alpha (HNF-4alpha) acts as an activator of redox-associated hepatocyte iNOS expression at the level of protein, mRNA, and promoter activation. In the absence of HNF-4alpha, this redox-mediated enhancement is ablated. HNF-4alpha functional activity is associated with a unique serine/threonine kinase-mediated phosphorylation pattern. This suggests that a redox-sensitive kinase pathway targets HNF-4alpha to augment hepatocyte iNOS expression. Previous studies have not addressed a redox-dependent kinase signaling pathway that targets HNF-4alpha and enhances hepatocyte iNOS gene transcription. A unique pattern of phosphorylation determines HNF-4alpha activity as a trans-activator of IL-1beta-mediated hepatocyte iNOS expression in the presence of oxidative stress.

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Published In

Am J Physiol Cell Physiol

DOI

ISSN

0363-6143

Publication Date

April 2003

Volume

284

Issue

4

Start / End Page

C1090 / C1099

Location

United States

Related Subject Headings

  • Transfection
  • Transcription Factors
  • Threonine
  • Serine
  • Rats
  • Promoter Regions, Genetic
  • Physiology
  • Phosphorylation
  • Phosphoproteins
  • Peptide Mapping
 

Citation

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Chicago
ICMJE
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Guo, H., Wei, J., Inoue, Y., Gonzalez, F. J., & Kuo, P. C. (2003). Serine/threonine phosphorylation regulates HNF-4alpha-dependent redox-mediated iNOS expression in hepatocytes. Am J Physiol Cell Physiol, 284(4), C1090–C1099. https://doi.org/10.1152/ajpcell.00394.2002
Guo, Hongtao, Junping Wei, Yusuke Inoue, Frank J. Gonzalez, and Paul C. Kuo. “Serine/threonine phosphorylation regulates HNF-4alpha-dependent redox-mediated iNOS expression in hepatocytes.Am J Physiol Cell Physiol 284, no. 4 (April 2003): C1090–99. https://doi.org/10.1152/ajpcell.00394.2002.
Guo H, Wei J, Inoue Y, Gonzalez FJ, Kuo PC. Serine/threonine phosphorylation regulates HNF-4alpha-dependent redox-mediated iNOS expression in hepatocytes. Am J Physiol Cell Physiol. 2003 Apr;284(4):C1090–9.
Guo, Hongtao, et al. “Serine/threonine phosphorylation regulates HNF-4alpha-dependent redox-mediated iNOS expression in hepatocytes.Am J Physiol Cell Physiol, vol. 284, no. 4, Apr. 2003, pp. C1090–99. Pubmed, doi:10.1152/ajpcell.00394.2002.
Guo H, Wei J, Inoue Y, Gonzalez FJ, Kuo PC. Serine/threonine phosphorylation regulates HNF-4alpha-dependent redox-mediated iNOS expression in hepatocytes. Am J Physiol Cell Physiol. 2003 Apr;284(4):C1090–C1099.

Published In

Am J Physiol Cell Physiol

DOI

ISSN

0363-6143

Publication Date

April 2003

Volume

284

Issue

4

Start / End Page

C1090 / C1099

Location

United States

Related Subject Headings

  • Transfection
  • Transcription Factors
  • Threonine
  • Serine
  • Rats
  • Promoter Regions, Genetic
  • Physiology
  • Phosphorylation
  • Phosphoproteins
  • Peptide Mapping