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Titolo:
Mitochondrial K-ATP channel activation reduces anoxic injury by restoring mitochondrial membrane potential
Autore:
Xu, MF; Wang, YG; Ayub, A; Ashraf, M;
Indirizzi:
Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA Univ Cincinnati Cincinnati OH USA 45267 Lab Med, Cincinnati, OH 45267 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
fascicolo: 3, volume: 281, anno: 2001,
pagine: H1295 - H1303
SICI:
0363-6135(200109)281:3<H1295:MKCARA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERMEABILITY TRANSITION PORE; ELECTRON-TRANSPORT CHAIN; CELL-DEATH; MYOCARDIAL-INFARCTION; POTASSIUM CHANNELS; INDUCED APOPTOSIS; CARDIAC MYOCYTES; ISCHEMIC-INJURY; REPERFUSION; DIAZOXIDE;
Keywords:
apoptosis; myocytes; ATP; permeability transition pore; cytochrome c;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Ashraf, M Univ Cincinnati, Dept Pathol & Lab Med, 231 Bethesda Ave, Cincinnati, OH 45267 USA Univ Cincinnati 231 Bethesda Ave Cincinnati OH USA 45267267 USA
Citazione:
M.F. Xu et al., "Mitochondrial K-ATP channel activation reduces anoxic injury by restoring mitochondrial membrane potential", AM J P-HEAR, 281(3), 2001, pp. H1295-H1303

Abstract

Mitochondrial membrane potential (Delta Psi (m)) is severely compromised in the myocardium after ischemia-reperfusion and triggers apoptotic events leading to cell demise. This study tests the hypothesis that mitochondrial ATP-sensitive K+ (mitoK(ATP)) channel activation prevents the collapse of Delta Psi (m) in myocytes during anoxia-reoxygenation (A-R) and is responsible for cell protection via inhibition of apoptosis. After 3-h anoxia and 2-hreoxygenation, the cultured myocytes underwent extensive damage, as evidenced by decreased cell viability, compromised membrane permeability, increased apoptosis, and decreased ATP concentration. Mitochondria in A-R myocyteswere swollen and fuzzy as shown after staining with Mito Tracker Orange CMTMRos an in an electron microscope and exhibited a collapsed Delta Psi (m),as monitored by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Cytochrome c was released from mitochondria into the cytosol as demonstrated by cytochrome c immunostaining. Activation of mitoKATP channel with diazoxide (100 mu mol/l) resulted in a significant protection against mitochondrial damage, ATP depletion, cytochrome c loss, and stabilized This protection was blocked by 5-hydroxydecanoate (500 mu mol/l),a mitoK(ATP) channel-selective inhibitor, but not by HMR-1098 (30 mu mol/l), a putative sarcolemmal K-ATP channel-selective inhibitor. Dissipation ofDelta Psi (m) also leads to opening of mitochondrial permeability transition pore, which was prevented by cyclosporin A. The data support the hypothesis that A-R disrupts Delta Psi (m) and induces apoptosis, which are prevented by the activation of the mitoK(ATP) channel. This further emphasizes the therapeutic significance of mitoKATP channel agonists in the prevention of ischemia-reperfusion cell injury.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 07:31:19