Zinc protects human kidney cells from depleted uranium-induced apoptosis

Depleted uranium (DU) is a weak radioactive heavy metal, and zinc (Zn) is an effective antidote to heavy metal poisoning. However, the effect of Zn on DU-induced cytotoxicity and apoptosis is not completely understood. The purpose of this study was to evaluate the effect of Zn on DU-induced cell apoptosis in human kidney cells (HK-2) and explore its molecular mechanism. Pre-treatment with Zn significantly inhibited DU-induced apoptosis. It reduced the formation of reactive oxygen species in the cells, increased the catalase (CAT) and glutathione (GSH) concentrations, suppressed the DU-induced soluble Fas receptor (sFasR) and soluble Fas ligand (sFasL) overexpression, suppressed the release of cytochrome c and apoptosis inhibitor factor (AIF) from mitochondria to cytoplasm, inhibited the activation of caspase-9, caspase-8 and caspase-3, and induced metallothionein (MT) expression. Furthermore, exogenous MT effectively inhibited DU-induced cell apoptosis. In conclusion, mitochondrial and FasR-mediated apoptosis pathways contribute to DU-induced apoptosis in HK-2 cells. Through independent mechanisms, such as indirect antioxidant effects, inhibition of the activation of caspase-9, caspase-8 and caspase-3, and induction of MT expression, Zn inhibits DU-induced apoptosis.