Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1

EMBO J. 1991 Aug;10(8):2247-58.

Abstract

Hydrogen peroxide and oxygen radicals are agents commonly produced during inflammatory processes. In this study, we show that micromolar concentrations of H2O2 can induce the expression and replication of HIV-1 in a human T cell line. The effect is mediated by the NF-kappa B transcription factor which is potently and rapidly activated by an H2O2 treatment of cells from its inactive cytoplasmic form. N-acetyl-L-cysteine (NAC), a well characterized antioxidant which counteracts the effects of reactive oxygen intermediates (ROI) in living cells, prevented the activation of NF-kappa B by H2O2. NAC and other thiol compounds also blocked the activation of NF-kappa B by cycloheximide, double-stranded RNA, calcium ionophore, TNF-alpha, active phorbol ester, interleukin-1, lipopolysaccharide and lectin. This suggests that diverse agents thought to activate NF-kappa B by distinct intracellular pathways might all act through a common mechanism involving the synthesis of ROI. ROI appear to serve as messengers mediating directly or indirectly the release of the inhibitory subunit I kappa B from NF-kappa B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • Cycloheximide / pharmacology
  • DNA / metabolism
  • Enhancer Elements, Genetic
  • Free Radicals
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Hydrogen Peroxide / chemistry*
  • Interleukin-1 / metabolism
  • Lectins / metabolism
  • Lipopolysaccharides / metabolism
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Oxygen / chemistry*
  • Promoter Regions, Genetic
  • Protein Kinase C / metabolism
  • RNA, Double-Stranded / metabolism
  • T-Lymphocytes / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Virus Replication

Substances

  • Free Radicals
  • Interleukin-1
  • Lectins
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Double-Stranded
  • Tumor Necrosis Factor-alpha
  • DNA
  • Cycloheximide
  • Hydrogen Peroxide
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • Oxygen