Cytoprotective effect of bis(1-oxy-2-pyridinethiolato)oxovanadiun(IV) on myocardial ischemia/reperfusion injury elicits inhibition of Fas ligand and Bim expression and elevation of FLIP expression.
Eur J Pharmacol
; 571(2-3): 180-8, 2007 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-17658509
ABSTRACT
VO(OPT), bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), has been shown to increase tyrosine phosphorylation of proteins and promote the insulin receptor signaling, thereby elicit anti-diabetic action. We here investigated the cytoprotective action of VO(OPT) on myocardial infarction and cardiac functional recovery in rats subjected to myocardial ischemia/reperfusion and defined mechanisms underlying its cytoprotective action. Rats underwent 30 min myocardial ischemia by left anterior descending coronary artery occlusion followed by 24 h reperfusion. Post-ischemic treatment with VO(OPT) significantly reduced infarct size and improved cardiac function (left ventricular developed pressure and +/-dP/dt) after 72 h reperfusion and in a dose-dependent manner. Moreover, VO(OPT) treatment also dose-dependently significantly inhibited caspases-3, -9 and -7 processing, thereby elicited the anti-apoptotic effect. The cytoprotective effect of VO(OPT) was closely associated with restoration of Akt activity. The recovered Akt activity correlated with increased phosphorylation of Bad and forkhead transcription proteins, thereby inhibiting apoptotic signaling. Furthermore, treatment with VO(OPT) significantly increased FLIP expression, and decreased expression of Fas ligand and Bim in cardiomyocytes. Taken together, cardiomyocytes rescue following post-treatment with VO(OPT) from ischemia/reperfusion injury was mediated by increased FLIP expression and decreased Fas ligand and Bim expression via activation of Akt. These results demonstrate that treatment with VO(OPT) exerts significant cytoprotective effects along with improvement of cardiac functional recovery.
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Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Cardiotônicos
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Traumatismo por Reperfusão Miocárdica
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Proteínas Proto-Oncogênicas
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Citoproteção
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Proteínas Reguladoras de Apoptose
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Proteína Ligante Fas
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Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD
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Proteínas de Membrana
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Infarto do Miocárdio
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article