SUPEROXIDE-DISMUTASE DELAYS NEURONAL APOPTOSIS - A ROLE FOR REACTIVE OXYGEN SPECIES IN PROGRAMMED NEURONAL DEATH

Sympathetic neurons in culture die by apoptosis when deprived of nerve growth factor (NGF). We used this model of programmed cell death to s tudy the mechanisms that mediate neuronal apoptosis. Cultured sympathe tic neurons were injected with copper/zinc superoxide dismutase protei n (SOD) or with an expression vector containing an SOD cDNA. In both c ases apoptosis was delayed when the neurons were deprived of NGF. The delay was similar to that seen when a bcl-2 expression vector was inje cted. SOD, injected 8 hr after NGF deprivation, provided no protection , indicating that superoxide production may occur early in response to trophic factor deprivation. We have demonstrated, with a redox sensit ive dye, an increase in reactive oxygen species (ROS) that peaked at 3 hr after sympathetic neurons were deprived of NGF. If NGF was added b ack to the culture medium after the period of peak ROS generation, apo ptosis was completely prevented, suggesting that ROS production serves as an early signal, rather than a toxic agent, to mediate apoptosis.