The rescuing effect of nerve growth factor is the result of up-regulation of bcl-2 in hyperoxia-induced apoptosis of a subclone of pheochromocytoma cells, PC12h

The rat pheochromocytoma cell line PC12 is useful for studying neuronal cell differentiation since this cell line differentiates into neuronlike cells in response to nerve growth factor (NGF), We demonstrated that PC12h cells, a subclone of PC12 cells, died under hyperoxia (50% O-2) This cell death did not occur in the presence of antioxidant reagents. In the dead cells, DNA fragmentation and chromatin condensation were observed, suggesting that hyperoxia-induced apoptosis via reactive oxygen species (ROS). NGF effectively suppressed this hyperoxia-induced apoptosis. Accordingly, the amounts of bcl-2, a proto-oncogene product, increased in the cells rescued from apoptosis by NGF, Furthermore, bcl-2 antisense oligonucleotide canceled this rescuing effect of NGF. The present findings indicate that NGF rescues PC12h cells from hyperoxia-induced apoptosis via up-regulation of bcl-2. (C) 1997 Elsevier Science Ireland Ltd.