Cytoprotective Effect of Zinc-Mediated Antioxidant Gene Expression on Cortisol-Induced Cytotoxicity

摘要

The protective effect of zinc against cortisol-induced cell injury was examined in rainbow trout gill epithelial cells. Cells exposed to cortisol for 24 h showed increased leakage of lactate dehydrogenase (LDH) as well as decreased cell viability in adose-dependent manner. Treatment with zinc (100 muM ZnS0_4) reduced the severity of both LDH release and cell death as well as protected cells against cortisol-induced caspase-3 activation, indicating reduction of apoptosis. Cortisol-induced cell death,leakage of LDH, and caspase-3 activation were blocked by the glucocorticoid receptor antagonist Mifepristone (RU-486), suggesting that cell injury was cortisol-dependent. In addition, we studied the effect of zinc on the expression of antioxidant genessuch as metallothionein A (MTA), metallothionein B (MTB), glutathione-5'-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD) during cortisol-induced cell injury. MTA, MTB, GST, and G6PD mRNA levels increased after treatment with zinc or cortisol, separately or in combination. Higher mRNA levels of MTA, MTB, GST, and G6PD were detected when cells were treated with 100 muM ZnS04 and 1 muM cortisol in combination at the same time compared to treatment with zinc or cortisol separately. Cells treated with zinc showed increased intracellular free zinc concentrations, and this response was significantly enhanced in cells treated with cortisol and zinc. In conclusion, zinc treatment inhibited cortisol-induced cytotoxicity and apoptosis through indirect antioxidant action.