Document 0854
 DOCN  M9650854
 TI    Dose-dependent opposite effect of zinc on apoptosis in mouse thymocytes.
 DT    9605
 AU    Provinciali M; Di Stefano G; Fabris N; Gerontology Research Department,
       Italian National Research; Centres on Aging (INRCA), Ancona, Italy.
 SO    Int J Immunopharmacol. 1995 Sep;17(9):735-44. Unique Identifier :
       AIDSLINE MED/96153668
 AB    Zinc is a crucial nutritional component required for the normal
       development and maintenance of immune functions. It has been reported
       that zinc is a potent inhibitor of DNA fragmentation, the specific
       marker of apoptosis. The effect of zinc on apoptotic cell death has been
       previously studied in a narrow range of high zinc concentrations, and
       the role of physiological zinc doses has not yet been elucidated. In
       this paper we evaluate the effect of in vitro Zn2+ administration at
       concentrations higher than, corresponding to, and lower than the
       physiological concentration, in thymocytes from young mice. We
       demonstrate that Zn2+ has an opposite effect on apoptosis, inhibiting or
       increasing it depending on the Zn2+ concentration used. High Zn2+
       concentrations (from 600 to 75 microM) inhibit both serum-free medium
       and DEX-induced thymocyte apoptosis. Low Zn2+ concentrations (from 15 to
       7.5 microM) induce apoptosis or increase serum-free medium-induced
       apoptosis. The effect of low Zn2+ concentrations on DEX-induced
       apoptosis is dependent on the length of incubation, since Zn2+ has an
       additive effect with DEX in inducing DNA fragmentation at 8 h of
       culture, whereas it blocks DEX-induced apoptosis after 20 h incubation.
       Both DEX and 15 microM Zn(2+)-induced DNA fragmentation require protein
       synthesis, being blocked through cycloheximide. The inhibiting and
       inducing effects of Zn2+ on apoptosis are exerted on G0/G1 phase
       thymocytes. The inhibiting effect of Zn2+ on apoptosis is related to an
       increase in the number of CD4+CD8+ thymocytes. Concentrations of Zn2+
       inducing apoptosis sometimes cause a decrease of CD4+CD8+ cells with a
       corresponding increase of CD4+CD8-thymocytes. These data show that in
       vitro Zn2+ has a dose-dependent opposite effect on apoptosis, suggesting
       that Zn2+ not only acts as an inhibitor but also plays a more complex
       role in physiological intrathymic cell selection.
 DE    Analysis of Variance  Animal  Apoptosis/DRUG EFFECTS  Culture Media,
       Serum-Free  CD4-Positive T-Lymphocytes/DRUG EFFECTS  CD8-Positive
       T-Lymphocytes/DRUG EFFECTS  Dexamethasone/ANTAGONISTS & INHIB
       Dose-Response Relationship, Drug  Flow Cytometry  Male  Mice  Mice,
       Inbred BALB C  Support, Non-U.S. Gov't  T-Lymphocytes/*DRUG EFFECTS
       Zinc/*PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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