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. 1994 Apr 26;91(9):3619–3622. doi: 10.1073/pnas.91.9.3619

Redox regulation of signal transduction: tyrosine phosphorylation and calcium influx.

F J Staal 1, M T Anderson 1, G E Staal 1, L A Herzenberg 1, C Gitler 1, L A Herzenberg 1
PMCID: PMC43632  PMID: 7513425

Abstract

Studies presented here show that altering the intracellular redox balance by decreasing glutathione levels profoundly affects early signal transduction events in human T cells. In a T-cell receptor (TCR) signaling model, short-term pretreatment with buthionine sulfoximine, which specifically decreases intracellular glutathione, essentially abrogates the stimulation of calcium influx by anti-CD3 antibodies without significantly impairing other aspects of TCR-initiated signal transduction, such as overall levels of TCR-stimulated tyrosine phosphorylation. In an inflammatory-cytokine signaling model, the failure of tumor necrosis factor alpha to stimulate more than minimal tyrosine phosphorylation in lymphocytes is overcome by buthionine sulfoximine pretreatment--i.e., tumor necrosis factor alpha stimulates extensive tyrosine phosphorylation in glutathione-depleted lymphocytes. These redox-dependent changes in T-cell responsiveness suggest that the glutathione deficiency that we and others have demonstrated in human immunodeficiency virus-infected individuals may contribute significantly to the immunodeficiency and the increased inflammatory reactions in these individuals.

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Selected References

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