Dual effect of nitric oxide on cell death : Induction and protection of apoptosis

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We investigated the protective effect of nitric oxide (NO) at a low concentration on cell death induced by NO and its mechanism in human neuroblastoma SH-SY5Y cells and mouse macrophage cell line, RAW264.Sodium nitroprusside (SNP), an NO donor, induced cell death in SH-SY5Y cells. Pretreatment with NOC12, an NO donor, at a low concentration partially prevented the cell death induced by SNP. Pretreatment with cyclic GMP analogues, dibutyryl-cGMP, prevented SNP-induced cell death. NOC12 at a low concentration, which has no effect on the cell viability, induced cell death in the presence of a guanylate cyclase inhibitor, LY83583. The cell death was partially protected by dibutyryl-cGMP. These results suggest that cGMP has a protective effect on NO-induced cell death in SH-SY5Y cells.Pretreatment with 100 μM SNP for 24h prevented the cell death and cytochrome c release induced by 4 mM SNP in RAW264 cells. The effect of SNP pretreatment was reduced by LY83583 (guanylyl cyclase inhibitors). Pretreatment with DBcGMP prevented cell death induced by NOC18, GSNO or SNP, in a concentration- dependent manner. Pretreatment with DBcGMP prevented cytochrome c release induced by NO donors. The protective effect of SNP or DBcGMP was significantly attenuated by KT5823 (a protein kinase G inhibitor). These results indicate that NO at a low concentration protects RAW264 cells from the cytotoxicity of NO through cGMP production and activation of PKG.