Nitric oxide delays the death of trophic factor-deprived PC12 cells and sympathetic neurons by a cGMP-mediated mechanism.

摘要: We have used cultured PC12 cells and rat sympathetic neurons as model systems to examine the regulation of neuronal cell death survival. Because nitric oxide (NO) may be involved in nerve growth factor (NGF) signaling cells, we tested NO-generating compounds for their ability protect from after withdrawal trophic support. Three such agents, S-nitroso-N- acetylpenicillamine (SNAP), diethylenetriamine NO adduct (DETA-NO), sodium nitroprusside provide (SNP), were found promote complete short-term survival removal serum naive NGF neuronally differentiated neurons. One major target action is guanylate cyclase, which activated by nitrosylation its heme prosthetic group. observed that inhibition cyclase blocks protective effects generators on factor-deprived without preventing NGF-induced also permeant cGMP analogs an inhibitor cGMP-specific phosphodiesterase enhance survival, suggesting are mediated activation increased intracellular cGMP. N-Nitro-L-arginine methyl ester, a synthase inhibitor, did not block NGF-promoted or neuron These findings indicate like NGF, has survival- promoting actions but two agents work initially independent mechanisms.