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Modulation of transcription factor NFχB activity by intracellular glutathione levels and by variations of the extracellular cysteine supply
Author(s) -
Mihm Sabine,
Galter Dagmar,
Dröge Wulf
Publication year - 1995
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.9.2.7781927
Subject(s) - glutathione , intracellular , extracellular , cysteine , cystine , transcription factor , glutathione disulfide , biochemistry , microbiology and biotechnology , chemistry , biology , gene , enzyme
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 NFχB, whereas incubation with increasing extracellular concentrations of cysteine inhibits the DNA‐binding and transactivating activity of NFχB. 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. NFχB 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., Galter, D., Dröge, W. Modulation of transcription factor NFχB activity by intracellular glutathione levels and by variations of the extracellular cysteine supply. FASEB J. 9, 246–252 (1995)