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

Md Shenuarin Bhuiyan, Masatoshi Shibuya, Norifumi Shioda, Shigeki Moriguchi, Jiro Kasahara, Yosiharu Iwabuchi, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)180-188
Number of pages9
JournalEuropean Journal of Pharmacology
Volume571
Issue number2-3
DOIs
Publication statusPublished - 2007 Oct 1

Keywords

  • Cardioprotection
  • Ischemia/reperfusion
  • Protein kinase B (Akt)
  • VO(OPT)

ASJC Scopus subject areas

  • Pharmacology

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