EXPRESSION OF HUMAN COPPER ZINC-SUPEROXIDE DISMUTASE INHIBITS THE DEATH OF RAT SYMPATHETIC NEURONS CAUSED BY WITHDRAWAL OF NERVE GROWTH-FACTOR/

Rat superior cervical ganglion neurons require the presence of nerve g rowth factor (NGF) to develop and survive in culture. If NGF is remove d from the culture medium, then the neurons die of programmed cell dea th. We investigated the potential role of Ca2+ and reactive oxygen spe cies in this process. We found that overexpression of human wild-type copper/zinc-superoxide dismutase in cultured superior cervical ganglio n neurons, using an adenovirus-based vector, substantially protected t he cells from the effects of NGF withdrawal, although overexpression o f the Ca2+-binding protein calbindin D-28k or the enzyme beta-galactos idase did not. We also observed that treatment of the cells with the c ytokine transforming growth factor-beta(1), which has been shown to pr otect neurons against oxidative injury, delayed cell death produced by NGF withdrawal. These data suggest a role for reactive oxygen species in triggering programmed cell death of rat sympathetic neurons upon g rowth factor withdrawal.