H2O2 opens mitochondrial KATP channels and inhibits GABA receptors via protein kinase C- in cardiomyocytes
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چکیده
Zhang, Hong Yan, Bradley C McPherson, Huiping Liu, Timir S Baman, Peter Rock, and Zhenhai Yao. H2O2 opens mitochondrial KATP channels and inhibits GABA receptors via protein kinase Cin cardiomyocytes. Am J Physiol Heart Circ Physiol 282: H1395–H1403, 2002; 10.1152/ajpheart.00683.2001.—Oxygen radicals and protein kinase C (PKC) mediate ischemic preconditioning. Using a cultured chick embryonic cardiomyocyte model of hypoxia and reoxygenation, we found that the oxygen radicals generated by ischemic preconditioning were H2O2. Like preconditioning, H2O2 selectively activated the -isoform of PKC in the particulate compartment and increased cell viability after 1 h of hypoxia and 3 h of reoxygenation. The glutathione peroxidase ebselen (converting H2O2 to H2O) and the superoxide dismutase inhibitor diethyldithiocarbamic acid abolished the increased H2O2 and the protection of preconditioning. PKC activation with phorbol 12-myristate 13-acetate increased cell survival; the protection of preconditioning was blocked by V1–2, a selective PKCantagonist. Similar to preconditioning, the protection of PKC activation was abolished by mitochondrial KATP channel blockade with 5-hydroxydecanoate or by GABA receptor stimulation with midazolam or diazepam. In addition, PKC, mitochondrial ATP-sensitive K (KATP) channels, and GABA receptors had no effects on H2O2 generated by ischemic preconditioning before prolonged hypoxia and reoxygenation. We conclude that H2O2 opens mitochondrial KATP channels and inhibits GABA receptors via activating PKC. Through this signal transduction, preconditioning protects ischemic cardiomyocytes.
منابع مشابه
Protection of cardiac myocytes via d1-opioid receptors, protein kinase C, and mitochondrial KATP channels
Huh, Joon, Garrett J. Gross, Hiroshi Nagase, and Bruce T. Liang. Protection of cardiac myocytes via d1-opioid receptors, protein kinase C, and mitochondrial KATP channels. Am J Physiol Heart Circ Physiol 280: H377–H383, 2001.—The objective of the present study was to investigate the role of d1-opioid receptors in mediating cardioprotection in isolated chick cardiac myocytes and to investigate w...
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