TY - JOUR
T1 - Dose-dependent opposite effect of zinc on apoptosis in mouse thymocytes
AU - Provinciali, Mauro
AU - Stefano, Giuseppina Di
AU - Fabris, Nicola
PY - 1995
Y1 - 1995
N2 - 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.
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 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.
KW - apoptosis
KW - mouse
KW - thymocytes
KW - zinc
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U2 - 10.1016/0192-0561(95)00063-8
DO - 10.1016/0192-0561(95)00063-8
M3 - Article
C2 - 8582785
AN - SCOPUS:0028819948
VL - 17
SP - 735
EP - 744
JO - International Journal of Immunopharmacology
JF - International Journal of Immunopharmacology
SN - 0192-0561
IS - 9
ER -