Zinc and Copper inhibit nerve growth factor-mediated protection from oxidative stress-induced apoptosis

Abstract We have previously provided evidence that two transition metal cations, Zn 2+ and Cu 2+ , can alter the conformation of nerve growth factor (NGF), rendering it unable to bind to its receptors or to activate signal transduction pathways. In the present study, we have assessed the influence of Zn 2+ and Cu 2+ on NGF-mediated protection from an oxidative insult. Exposure of rat pheochromocytoma (PC12) cells to hydrogen peroxide resulted in an increase in cell death via apoptosis, which was inhibited by NGF. Zn 2+ and Cu 2+ , when added to cultures at a concentration of 100 μ M, prevented NGF-mediated survival-promoting effects. Neither of these ions had an effect on basal cell viability (in the absence of NGF) after an oxidative insult. These results demonstrate that Zn 2+ and Cu 2+ can selectively inhibit NGF-mediated resistance to an oxidative stress, and have significant implications for neuronal function under both physiological and pathological (e.g. cerebral ischemia) conditions.