Redox regulation of the rat hepatocyte iNOS promoter.

Journal Article (Journal Article)

BACKGROUND: The purpose of this study was to define the redox sensitive cis-acting transcriptional mechanisms that regulate inducible nitric oxide synthase (iNOS) promoter function in the hepatocyte. METHODS: Clonal deletion constructs of the rat hepatocyte iNOS promoter (Genbank X95629; 1845 base pair)-reporter plasmid were transiently transfected into HepG2 cells treated with IL-1 beta and IL-1 beta + hydrogen peroxide. RESULTS: A segment of the promoter upstream from nucleotide -1126 was associated with redox-sensitive augmentation of promoter activity. Site-directed mutagenesis of 2 antioxidant response elements (AREs) was combined with transfection analysis to demonstrate that mutation of the ARE at nt-1347 ablated oxidant stress-mediated activation of the iNOS promoter. CONCLUSIONS: This ARE conveys the redox-sensitive response of the rat iNOS promoter. Hepatocyte iNOS expression is a novel and, as yet, poorly described antioxidant mechanism that is cytokine and redox sensitive and that plays a pleuripotent regulatory role in hepatocellular function in the face of sepsis and shock.

Full Text

Duke Authors

Cited Authors

  • Punzalan, C; Cai, C; Schroeder, RA; Kuo, PC

Published Date

  • August 1999

Published In

Volume / Issue

  • 126 / 2

Start / End Page

  • 450 - 455

PubMed ID

  • 10455920

International Standard Serial Number (ISSN)

  • 0039-6060


  • eng

Conference Location

  • United States