Cyclic GMP-dependent and -independent regulation of MAP kinases by sodium nitroprusside in isolated cardiomyocytes.
Sodium nitroprusside (SNP) elicits various physiological effects, in part through generation of the membrane permeable mediator nitric oxide (NO). In the heart, besides its role in regulating contractility, NO is involved in both protection from and induction of cellular damage. The present study investigated the role of SNP in the regulation of the mitogen-activated protein kinases (MAPKs) in isolated adult rat cardiomyocytes. SNP maximally activated Erk1, Erk2, p38 MAPK and MAPKAPK2 in 5-10 min. The activation of MAPKAPK2 by SNP was blocked by the soluble guanylyl cyclase inhibitor, 1H-[1, 2,4]oxadiazolol[4,3-a]quinoxalin-1-one (ODQ) and the p38 MAPK inhibitor, SB203580. The activation of Erk1 was insensitive to ODQ but completely blocked by the Mek1 inhibitor PD98059. The membrane-permeable homologue of cGMP, 8-Br-cGMP, also activated p38 MAPK (A(0.5) approximately 50 microM) but not Erk1 and Erk2. These results indicate that p38 MAPK and MAPKAPK2 are activated by SNP in cGMP-dependent pathways, while the Erk1 activation by SNP is independent of cGMP levels.
Kim
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Department of Medicine, University of British Columbia, Rm S125, 2nd Floor, Koerner Pavilion, 2211 Wesbrook Mall, Vancouver, B.C., Canada.
Xu
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Katz
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Pelech
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D009599:Nitroprusside / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2
D000959:Antihypertensive Agents; D006152:Cyclic GMP; D047908:Intracellular Signaling Peptides and Proteins; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009599:Nitroprusside; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C016276:8-bromocyclic GMP