Cyclic adenosine monophosphate inhibits nitric oxide-induced apoptosis of cardiac muscle cells in a c-Jun N-terminal kinase-dependent manner.
Cyclic adenosine monophosphate (cAMP) modulates various agent-induced apoptosis. In this study, we observed that cAMP had a significantly protective effect on nitric oxide (NO)-induced cytotoxicity in H9c2 cardiac muscle cells. Pretreatment with DBcAMP (cAMP analogue) or forskolin (adenylyl cyclase activator) also significantly prevented the SNP-induced apoptosis in H9c2 cells. In contrast, H-89 or KT5720 (PKA inhibitor) reversed the protective effects of DBcAMP. In this study, DBcAMP or forskolin reduced SNP-induced JNK/SAPK activation to the basal level, but KT5720 reversed the inhibitory effects of these two agents. In contrast to JNK/SAPK activation, DBcAMP and forskolin significantly enhanced SNP-activated p38 MAPK phosphorylation and did not affect SNP-mediated ERK activation. KT5720 reversed the effects of DBcAMP and forskolin on p38 MAPK phosphorylation. The inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK/SAPK markedly reduced the extent of SNP-induced cell death. Taken together, we suggest that JNK/SAPK is related to cAMP-protective effect in SNP-induced apoptosis. In addition, c-AMP relating agents protected SNP-induced cell death in neonatal rat ventricular cardiomyocytes. The cAMP-relating agent-induced protective effect is not restricted in H9c2 cardiac muscle cells.
Chae
Han-Jung
HJ
Department of Pharmacology and Institute of Cardiovascular Research, Chonbuk National University Medical School, South Korea.
Chae
Soo-Wan
SW
Kim
Hyung-Ryong
HR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D006690:Bisbenzimidazole / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000633:toxicity*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats
D009599:Nitroprusside; D005576:Colforsin; D009569:Nitric Oxide; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D006690:Bisbenzimidazole