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The FASEB Journal, Vol 9, 246-252, Copyright © 1995 by The Federation of American Societies for Experimental Biology


RESEARCH COMMUNICATIONS

Modulation of transcription factor NF kappa B activity by intracellular glutathione levels and by variations of the extracellular cysteine supply

S Mihm, D Galter and W Droge
Department of Immunochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

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.


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Copyright © 1995 by The Federation of American Societies for Experimental Biology.