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Titolo:
Role of protein kinase C in mitochondrial K-ATP channel-mediated protection against Ca2+ overload injury in rat myocardium
Autore:
Wang, YG; Ashraf, M;
Indirizzi:
Univ Cincinnati, Med Ctr, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA Univ Cincinnati Cincinnati OH USA 45267 Lab Med, Cincinnati, OH 45267 USA
Titolo Testata:
CIRCULATION RESEARCH
fascicolo: 10, volume: 84, anno: 1999,
pagine: 1156 - 1165
SICI:
0009-7330(19990528)84:10<1156:ROPKCI>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
ELICITS STRONG PROTECTION; CALCIUM PARADOX; PRECONDITIONING ELICITS; POTASSIUM CHANNEL; SIGNALING PATHWAY; HEART; ACTIVATION; DIAZOXIDE; MYOCYTES; CARDIOPROTECTION;
Keywords:
K+ channel; Ca2+ paradox; Ca2+ preconditioning; protein kinase C; diazoxide;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Ashraf, M Univti,ncinnati, Med Ctr, Dept Pathol & Lab Med, 231 Bethesda Ave, Cincinna Univ Cincinnati 231 Bethesda Ave Cincinnati OH USA 45267 incinna
Citazione:
Y.G. Wang e M. Ashraf, "Role of protein kinase C in mitochondrial K-ATP channel-mediated protection against Ca2+ overload injury in rat myocardium", CIRCUL RES, 84(10), 1999, pp. 1156-1165

Abstract

Growing evidence exists that ATP-sensitive mitochondrial potassium channels (MitoK(ATP) channel) are a major contributor to the cardiac protection against ischemia, Given the importance of mitochondria in the cardiac cell, we tested whether the potent and specific opener of the MitoK(ATP) channel diazoxide attenuates the lethal injury associated with Ca(2+)overload, The specific aims of this study were to test whether protection by diazoxide is mediated by MitoK(ATP) channels: whether diazoxide mimics the effects of Ca2+ preconditioning; and whether diazoxide reduces Ca2+ paradox (PD) injury via protein kinase C (PKC) signaling pathways. Langendorff-perfused rat hearts were subjected to the Ca2+ PD (10 minutes of Ca2+ depletion followed by10 minutes of Ca2+ repletion), The effects of the MitoK(ATP) channel and other interventions on functional, biochemical, and pathological changes in hearts subjected to Ca2+ PD were assessed. In hearts treated with 80 mu mol/L diazoxide, left ventricular end-diastolic pressure and coronary flow were significantly preserved after Ca2+ PD; peak lactate dehydrogenase releasewas also significantly decreased, although ATP content was less depleted. The cellular structures were well preserved, including mitochondria and intercalated disks in diazoxide-treated hearts compared with nontreated Ca2+ PD hearts. The salutary effects of diazoxide on the Ca2+ PD injury were similar to those in hearts that underwent Ca2+ preconditioning or pretreatment with phorbol 12-myristate 13-acetate before Ca2+ PD. The addition of sodium5-hydroxydecanoate, a specific MitoK(ATP) channel inhibitor, or chelerythrine chloride, a PKC inhibitor, during diazoxide pretreatment completely abolished the beneficial effects of diazoxide on the Ca2+ PD. Blockade of Ca2entry during diazoxide treatment by inhibiting L-type Ca2+ channel with verapamil or nifedipine also completely reversed the beneficial effects of diazoxide on the Ca2+ PD, PKC-delta was translocated to the mitochondria, intercalated disks, and nuclei of myocytes in diazoxide-pretreated hearts, andPKC-alpha and PKC-epsilon were translocated to sarcolemma and intercalateddisks, respectively. This study suggests that the effect of the MitoK(ATP)channel is mediated by PKC-mediated signaling pathway.

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Documento generato il 03/06/20 alle ore 09:33:10