Cytoprotective effect of sodium orthovanadate on ischemia/reperfusion- induced injury in the rat heart involves Akt activation and inhibition of fodrin breakdown and apoptosis

Yoko Takada, Masami Hashimoto, Jiro Kasahara, Kazuyuki Aihara, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

In a rat model of myocardial ischemic infarction, sodium orthovanadate rescued cells from ischemia/reperfusion injuries. Rats underwent 30 min of myocardial ischemia by occluding the left coronary artery followed by 24 h of reperfusion. Post-treatment with orthovanadate reduced infarct size in a dose-dependent manner. Orthovanadate treatment also ameliorated contractile dysfunction of the left ventricle 72 h after reperfusion. The cytoprotective action of orthovanadate treatment was closely associated with inhibition of fodrin breakdown. Since orthovanadate is a potent inhibitor for protein tyrosine phosphatases, thereby activating tyrosine kinases and phosphatidylinositol 3-kinase (PI3K) pathways, we investigated activities of protein kinase B (Akt), a downstream target of PI3K in cardiomyocytes. Orthovanadate-induced cytoprotection was associated with partial restoration of reduced Akt activity following myocardial infarction. Restoration of Akt activity by orthovanadate treatment correlated positively with increased phosphorylation of glycogen synthase kinase-3β and Bad in cardiomyocytes. Furthermore, orthovanadate treatment inhibited caspase-3 activation induced by ischemia. Taken together, orthovanadate post-treatment rescued cardiomyocytes from ischemia/reperfusion injuries via Akt activation and inhibition of fodrin breakdown, thereby inhibiting apoptosis.

Original languageEnglish
Pages (from-to)1249-1255
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume311
Issue number3
DOIs
Publication statusPublished - 2004 Dec 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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