Dose-dependent opposite effect of zinc on apoptosis in mouse thymocytes

Mauro Provinciali, Giuseppina Di Stefano, Nicola Fabris

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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 μM) inhibit both serum-free medium and DEX-induced thymocyte apoptosis. Low Zn2+ concentrations (from 15 to 7.5 μM) 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 μM Zn2+-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.

Original languageEnglish
Pages (from-to)735-744
Number of pages10
JournalInternational Journal of Immunopharmacology
Issue number9
Publication statusPublished - 1995


  • apoptosis
  • mouse
  • thymocytes
  • zinc

ASJC Scopus subject areas

  • Immunology
  • Pharmacology


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