Oxidative stress increases hepatocyte iNOS gene transcription and promoter activity.

Published

Journal Article

Hepatocyte expression of inducible nitric oxide synthase (iNOS) is initiated by the presence of pro-inflammatory cytokines, such as interleukin-1beta (IL-1). In the presence of oxidative stress, IL-1beta mediated hepatocyte iNOS expression and NO synthesis are significantly increased. To determine the underlying molecular mechanism responsible for oxidative stress augmentation of hepatocyte iNOS expression, rat hepatocytes in primary culture were stimulated with IL-1beta (250 U/mL) in the presence and absence of benzenetriol (BZT, 0-100 microM), an autocatalytic source of superoxide at physiologic pH. Nuclear runon analysis demonstrated that BZT was associated with increased iNOS gene transcription in the setting of IL-1 stimulation. Transient transfection of a plasmid construct composed of the rat hepatocyte iNOS promoter and a chloramphenicol transferase reporter gene demonstrated that the combination of BZT and IL-1 significantly increased iNOS promoter activity in comparison to that of IL-1beta alone. These data indicate that BZT-mediated oxidative stress increases IL-1beta induced iNOS gene transcription and iNOS promoter activity.

Full Text

Duke Authors

Cited Authors

  • Kuo, PC; Abe, KY; Schroeder, RA

Published Date

  • May 19, 1997

Published In

Volume / Issue

  • 234 / 2

Start / End Page

  • 289 - 292

PubMed ID

  • 9177260

Pubmed Central ID

  • 9177260

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1006/bbrc.1997.6562

Language

  • eng

Conference Location

  • United States