Nerve growth factor induces resistance of PC12 cells to nitric oxide cytotoxicity.

Nitric oxide (NO) donors, sodium nitroprusside and NOC 7, caused pheochromocytoma (PC12) cell death in a concentration and time-dependent manner. This cytotoxicity was blocked by the NO trapping agent, oxyhemoglobin. A membrane permeable cGMP analogue had no cytotoxicity in a reasonable concentration. Moreover, the selective inhibitor of cGMP-dependent protein kinase, KT5823, had no effect on NOC 7 cytotoxicity. These results suggest that NO caused PC12 cell death but not through the cGMP pathway. Additionally, this NO-induced PC12 cell death is not accompanied by DNA fragmentation. Nerve growth factor (NGF), which is able to rescue PC12 cells from serum deprivation, failed to protect PC12 cells from NO-induced cell death by acute treatment. However, PC12 cells differentiated by NGF treatment for more than 3 days did not die after NO exposure. The differentiated PC12 cells, but not undifferentiated cells, expressed NO synthase (NOS). NGF-differentiated PC12 cells acquired the resistance to NO, by a mechanism not yet identified, accompanied by the expression of NOS.