Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1.
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.
Schreck
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R
Laboratorium für Molekulare Biologie, Ludwig-Maximilians-Universität München, FRG.
Rieber
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P
Baeuerle
P A
PA
D001483:Base Sequence; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005609:Free Radicals; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry*; D007375:Interleukin-1 / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry*; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014779:Virus Replication
D005609:Free Radicals; D007375:Interleukin-1; D037102:Lectins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D003513:Cycloheximide; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen