PT  - JOURNAL ARTICLE
AU  - Yoko Takada
AU  - Masami Hashimoto
AU  - Jiro Kasahara
AU  - Kazuyuki Aihara
AU  - Kohji Fukunaga
TI  - Cytoprotective Effect of Sodium Orthovanadate on Ischemia/Reperfusion-Induced Injury in the Rat Heart Involves Akt Activation and Inhibition of Fodrin Breakdown and Apoptosis
AID  - 10.1124/jpet.104.070839
DP  - 2004 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1249--1255
VI  - 311
IP  - 3
4099  - http://jpet.aspetjournals.org/content/311/3/1249.short
4100  - http://jpet.aspetjournals.org/content/311/3/1249.full
SO  - J Pharmacol Exp Ther2004 Dec 01; 311
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics