Regulation of gamma-glutamylcysteine synthetase activity by nerve growth factor

Nerve growth factor is a neurotrophic factor that regulates neuronal cell development, maintenance, and injury responses in the peripheral and central nervous system. Nerve growth factor reduces injury owing to oxidative stress in rat pheochromocytoma (PC12) cells by increasing intracellular glutathione, in part owing to its stimulation of the activity of gamma-glutamylcysteine synthetase, which is the rate-limiting enzyme in the synthesis of glutathione. Here we show that nerve growth factor did not increase the activity of gamma-glutamylcysteine synthetase in PC12 cells at the transcriptional level. Rather, nerve growth factor enhanced the stability of gamma-glutamylcysteine synthetase mRNA in PC12 cells. These results suggest that, during oxidative stress, nerve growth factor extended the half-life of gamma-glutamylcysteine synthetase mRNA, thus increasing gamma-glutamylcysteine synthetase mRNA levels compared to nerve growth factor-deprived PC12 cells.