S. Mihm et al., MODULATION OF TRANSCRIPTION FACTOR NF-KAPPA-B ACTIVITY BY INTRACELLULAR GLUTATHIONE LEVELS AND BY VARIATIONS OF THE EXTRACELLULAR CYSTEINE SUPPLY, The FASEB journal, 9(2), 1995, pp. 246-252
HIV-infected individuals and SIV-infected rhesus macaques have, on the
average, decreased plasma cysteine and cystine concentrations and dec
reased 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 N
F kappa B, whereas incubation with increasing extracellular concentrat
ions of cysteine inhibits the DNA-binding and transactivating activity
of NF kappa B. Because inhibition of DNA-binding activity is associat
ed with increasing intracellular glutathione disulfide levels and GSSG
can be shown to inhibit the DNA-binding activity directly in cell-fre
e systems, our studies suggest that GSSG is a physiologically relevant
inhibitor in intact cells also, NF kappa B controls many immunologica
lly important genes, so our studies suggest that the immune system may
be sensitive not only against a cysteine and glutathione deficiency b
ut also against an excess of cysteine.