Antioxidant effect of retinoic acid on PC12 rat pheochromocytoma

Retinoic acid is a naturally occurring metabolite of vitamin A that influences the differentiation of a variety of neural cells in vitro. In the LA-N-1 human neuroblastoma line, retinoic acid treatment increases the binding of nerve growth factor (Bmax). The purpose of this study was to examine the effects of retinoic acid on PC12 rat pheochromocytoma, a neural crest-derived cell line that can be induced to express a sympathetic neuroblast-like phenotype by nerve growth factor treatment. In contrast to the differentiating effects of nerve growth factor, retinoic acid treatment of PC12 cells had a negligible effect on cellular morphology. However, treatment with retinoic acid enhanced the survival of PC12 cells following oxidative injury generated by H2O2 treatment in a manner that is qualitatively similar to that observed after nerve growth factor treatment. Also, there was an increase in 125I-nerve growth factor binding activity in solubilized PC12 membrane preparations derived from retinoic acid-treated PC12 cells. These data suggest that retinoic acid may play a role in neuronal development and in neuronal injury by stimulating the ability of neurons to cope with oxidative stress and/or by enhancing neuronal responsiveness to trophic factors such as the nerve growth factor.