The copper transport protein Atox1 promotes neuronal survival

Atox1, a copper transport protein, was recently identified as a copper depe ndent suppressor of oxidative damage in yeast lacking superoxide dismutase. We have previously reported that Atox1 in the rat brain is primarily expre ssed in neurons, with the highest levels in distinct neuronal subtypes that are characterized by their high levels of metal, like copper, iron, and zi nc. In this report, we have transfected the Atox1 gene into several neurona l cell lines to increase the endogenous level of Atox1 expression and have demonstrated that, under conditions of serum starvation and oxidative injur y, the transfected neurons are significantly protected against this stress. This level of protection is comparable with the level of protection seen w ith copper/zinc superoxide dismutase and the anti-apoptotic gene bcl-2 that had been similarly transfected. Furthermore, neuronal cell lines transfect ed with a mutant Atox1 gene, where the copper binding domain has been modif ied to prevent metal binding, do not afford protection against serum starva tion resulting in apoptosis. Therefore, Atox1 is a component of the cellula r pathways used for protection against oxidative stress.