Nitric oxide mediates protein kinase C isoform translocation in rat heart during postischemic reperfusion.
It is controversial whether nitric oxide (NO) is protective or deleterious against ischemia-reperfusion injury. We examined the effect of NO on PKC isoform translocation and protection against ischemia-reperfusion injury in perfused heart. An NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester, 3.0 microM), administered only during reperfusion but not during ischemia, inhibited the translocation of PKC-alpha, -delta and -epsilon isoforms to the nucleus-myofibril fraction and the translocation of PKC-alpha to the membrane fraction after ischemia (20 min) and reperfusion (10 min) in the perfused rat heart. NO donors, 3-morpholinosydnonimine (SIN-1) or S-nitroso-N-acetylpenicillamine (SNAP) activated purified PKC in vitro. SIN-1 also induced PKC isoform translocation in perfused heart. On the other hand, PKC selective inhibitor, calphostin C (0.2 microM) or chelerythrine (1.0 microM), aggravated the contractile dysfunction of ischemic heart during reperfusion, when they were perfused during reperfusion. These data suggest that NO generated during reperfusion following ischemia activates PKC isoforms and may protect the heart against contractile dysfunction in the perfused rat heart.
Department of Legal Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan. kyoshida@po.cc.yamaguchi-u.ac.jp
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Mizukami
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Kitakaze
D000818:Animals; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D016277:Ventricular Function, Left / Q000187:drug effects
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D019331:NG-Nitroarginine Methyl Ester