Modulation of transcription factor NF kappa B activity by intracellular glutathione levels and by variations of the extracellular cysteine supply.
HIV-infected individuals and SIV-infected rhesus macaques have, on the average, decreased plasma cysteine and cystine concentrations and decreased intracellular glutathione levels. We now show that a depletion of intracellular glutathione in a human T cell line (Molt-4) inhibits the activation and nuclear translocation of the transcription factor NF kappa B, whereas incubation with increasing extracellular concentrations of cysteine inhibits the DNA-binding and transactivating activity of NF kappa B. Because inhibition of DNA-binding activity is associated with increasing intracellular glutathione disulfide levels and GSSG can be shown to inhibit the DNA-binding activity directly in cell-free systems, our studies suggest that GSSG is a physiologically relevant inhibitor in intact cells also. NF kappa B controls many immunologically important genes, so our studies suggest that the immune system may be sensitive not only against a cysteine and glutathione deficiency but also against an excess of cysteine.
Mihm
S
S
Department of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Galter
D
D
Dröge
W
W
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D006678:HIV; D015658:HIV Infections / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism; D015302:Simian Immunodeficiency Virus; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013601:T-Lymphocytes; D015533:Transcriptional Activation / Q000187:drug effects
D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D013438:Sulfhydryl Compounds; D005978:Glutathione; D003545:Cysteine; D004229:Dithiothreitol; D019803:Glutathione Disulfide; D000111:Acetylcysteine