The effect of changes in thiol subcompartments on T-cell colony formation and cell cycle progression: relevance to AIDS.
Recently, it has been shown that intra- and extracellular thiol levels are significantly lower than normal even in the relatively early stages of human immunodeficiency virus (HIV) infection. It is plausible that this deficiency could contribute both to the loss of T-cell function and the ability to replenish T cells associated with HIV infection. We had previously reported that the T-cell colony-forming cell (T-CFC) is impaired in HIV infection and that it can be enhanced with the thiol compounds 2-mercaptoethanol (2-ME) and N-acetylcysteine (NAC). In this study, the effect of the thiol-depleting reagents buthionine sulfoximine, cyclohexene-1-one, and copper phenanthroline on T-CFC formation and cell cycle progression was determined in HIV+ subject and/or controls. All three reagents inhibited T-CFC formation and cell cycle progression with a suggestion that colony formation by cells from HIV+ subjects was more sensitive to the effects of thiol depletion. 2-ME and NAC enhanced effect of NAC did not appear to involve increased protein kinase C translocation. Our results suggest that oxidation of membrane thiols, as well as depletion of intracellular glutathione, inhibits T-CFC formation as well as cell cycle progression for mitogen-stimulated cells in bulk culture.
Levy
E M
EM
Department of Microbiology, Boston University School of Medicine, Massachusetts 02118.
Wu
J
J
Salibian
M
M
Black
P H
PH
D000111:Acetylcysteine / Q000494:pharmacology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D019328:Buthionine Sulfoximine; D002451:Cell Compartmentation; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003512:Cyclohexanones / Q000494:pharmacology; D006801:Humans; D008623:Mercaptoethanol / Q000494:pharmacology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D003512:Cyclohexanones; D013438:Sulfhydryl Compounds; D008717:Methionine Sulfoximine; C028215:2-cyclohexen-1-one; D019328:Buthionine Sulfoximine; D008623:Mercaptoethanol; D011493:Protein Kinase C; D000111:Acetylcysteine