Document 0105 DOCN M9590105 TI Modulation of transcription factor NF kappa B activity by intracellular glutathione levels and by variations of the extracellular cysteine supply. DT 9509 AU Mihm S; Galter D; Droge W; Department of Immunochemistry, Deutsches Krebsforschungszentrum,; Heidelberg, Germany. SO FASEB J. 1995 Feb;9(2):246-52. Unique Identifier : AIDSLINE MED/95301128 AB 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. DE Acetylcysteine/PHARMACOLOGY Animal Base Sequence Binding Sites Cell Line Cell Nucleus/METABOLISM Cysteine/*PHARMACOLOGY Dithiothreitol/PHARMACOLOGY Dose-Response Relationship, Drug Glutathione/ANALOGS & DERIVATIVES/*METABOLISM Human HIV HIV Infections/METABOLISM Kinetics Macaca mulatta Molecular Sequence Data NF-kappa B/*METABOLISM Oligodeoxyribonucleotides/METABOLISM Simian Acquired Immunodeficiency Syndrome/METABOLISM Sulfhydryl Compounds/METABOLISM SIV T-Lymphocytes Trans-Activation (Genetics)/DRUG EFFECTS JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).