Document 0039
 DOCN  M9460039
 TI    Redox regulation of signal transduction: tyrosine phosphorylation and
       calcium influx.
 DT    9408
 AU    Staal FJ; Anderson MT; Staal GE; Herzenberg LA; Gitler C; Herzenberg LA;
       Department of Genetics, Stanford University School of Medicine,; CA
       94305.
 SO    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3619-22. Unique Identifier :
       AIDSLINE MED/94224792
 AB    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.
 DE    Aluminum Compounds/PHARMACOLOGY  Antigens, CD3/PHYSIOLOGY
       Calcium/*PHYSIOLOGY  Cell Line  Cytokines/*PHARMACOLOGY
       Fluorides/PHARMACOLOGY  Glutathione/*METABOLISM  Human  In Vitro
       Oxidation-Reduction  Phosphoserine/METABOLISM
       Phosphothreonine/METABOLISM  Receptors, Antigen, T-Cell/*PHYSIOLOGY
       Signal Transduction  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  T-Lymphocytes/*PHYSIOLOGY  Terpenes/PHARMACOLOGY
       Tyrosine/*ANALOGS & DERIVATIVES/METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).