Nitric oxide and cyclic GMP as pro- and anti-apoptotic agents.

Abstract

Previously we showed that atrial natriuretic peptide (ANP) increases cGMP production in PC12 (sympathetic-neuron-like) cells, cGMP elevations increase survival of hippocampal neurons during glutamate toxicity and ANP-induced cGMP elevations prolongs survival of stressed PC12 cells, all suggesting cGMP mediates anti-apoptotic/pro-survival effects in neural cells. The objective was to use a new technology, capillary electrophoresis-laser-induced-fluorescence-detector (CE-LIF) to accurately measure nitric oxide (NO)-induced stimulation and ANP/cGMP-induced inhibition of apoptotic DNA fragmentation in PC12 and NG108-15 (cholinergic-neuron-like) cells. Apoptotic DNA fragmentation was quantified by CE-LIF. Sodium nitroprusside (SNP, 0.1-1.0 mM, 24 hours), NO donor, increased apoptotic DNA fragmentation in NG108-15 cells, but not PC12 cells (both with serum). In serum-deprived PC12 cells, ANP at 1, 10 and 100 nM inhibited apoptotic DNA fragmentation by 75.8%, 84.7%, and 94.1%, respectively. The data show that NO at higher levels induces apoptosis in NG108-15 cells, but not PC12 cells, indicating differences in susceptibility to NO-induced toxicity, and that ANP-induced cGMP elevation is a potent and effective inhibitor of apoptosis in PC12 cells. The data suggest that NO-induced cGMP elevations in certain neural cells (e.g. PC12 cells) provide a protective (anti-apoptotic) mechanism that counter-balances the pro-apoptotic actions of NO, thus helping to limit damage caused by NO.