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Nitric oxide at a low concentration protects murine macrophage RAW264 cells against nitric oxide‐induced death via cGMP signaling pathway
Author(s) -
Yoshioka Y,
Yamamuro A,
Maeda S
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705206
Subject(s) - sodium nitroprusside , nitric oxide , cyclic guanosine monophosphate , programmed cell death , cgmp dependent protein kinase , apoptosis , cytochrome c , protein kinase a , mitochondrion , guanosine , cytosol , chemistry , microbiology and biotechnology , biochemistry , kinase , pharmacology , biology , enzyme , mitogen activated protein kinase kinase , organic chemistry
We investigated the cytoprotective effect of low‐dose nitric oxide (NO) on NO‐induced cell death in mouse macrophage‐like cell line RAW264. Sodium nitroprusside (SNP), an NO donor, at a high concentration (4 m M ) released cytochrome c from mitochondria and induced death in RAW264 cells. Acetyl‐ L ‐aspartyl‐ L ‐glutamyl‐ L ‐valyl‐ L ‐aspart‐1‐al (Ac‐DEVD‐CHO, 100–200 μ M ), a caspase‐3 inhibitor, attenuated the SNP‐induced cell death in a concentration‐dependent manner. Pretreatment with 100 μ M SNP for 24 h, which had no effect on cell viability, attenuated the cell death and reduced cytochrome c release from mitochondria to the cytosol induced by 4 m M SNP. LY83583 (1–3 μ M ) and 1 H ‐[1,2,4]oxadiazolo[4,3,‐a]quinoxalin‐1‐one (ODQ, 30–100 μ M ), soluble guanylate cyclase inhibitors, negated the protective effect of the 100 μ M SNP pretreatment. Pretreatment with 1 m M dibutylyl guanosine‐3′,5′‐cyclic monophosphate (DBcGMP), a cell‐permeable guanosine‐3′,5′‐cyclic monophosphate (cGMP) analogue, for 24 h inhibited both cytochrome c release and cell death induced by SNP. Protein kinase G inhibitor KT5823 (10 μ M ) significantly reduced the cytoprotective effects of low‐dose SNP and DBcGMP. These results indicate that low‐dose NO protects RAW264 cells from NO‐induced apoptosis through cGMP production and activation of protein kinase G.British Journal of Pharmacology (2003) 139 , 28–34. doi: 10.1038/sj.bjp.0705206