The inhibitory effect of zinc on cadmium-induced cell apoptosis and reactive oxygen species (ROS) production in cell cultures

Abstract

The prevention of apoptosis by Zn(2+) is a well-known phenomenon. Both in in vitro and in vivo Zn(2+) supplementation prevents apoptosis induced by a variety of agents, among them by cadmium ions. The target for protective action of Zn ions on cell apoptosis is still unknown. In this paper we have evaluated the effect of in vitro ZnCl(2) supplementation at a concentration corresponding to the physiological level (10 microM) and higher (50 microM), on apoptosis induced with different Cd concentrations in two cell types: HeLa human tumor cell line and bovine aorta endothelial cells (BAECs). We demonstrated that Zn supplementation, especially at 10 microM concentration, significantly inhibited apoptosis in both types of cells. To assess the mechanism involved in the Zn effect we examined the influence of Zn supplementation on Cd accumulation in cells, Cd-induced superoxide anion (O(2)(-)) and hydrogen peroxide (H(2)O(2)) production. Zn caused 1.2-2.0-fold inhibition of Cd accumulation, 1.2-2.0-fold inhibition of Cd-induced apoptotic cell death, 1.1-2.0-fold decrease in reactive oxygen species (ROS) production in HeLa cells and in BAECs. These results indicate that inhibition of Cd-induced apoptosis in cells by Zn might be due, not only by inhibition of Cd accumulation in cells but, at least in part, to inhibition of Cd-induced production of ROS, which in turn are known as strong inducers of apoptosis.