title: Ischemic postconditioning mediates cardioprotection via PI3K/GSK-3β/β-catenin signaling pathway in ischemic rat myocardium.
abstract: Previous studies have shown that PI3K/GSK-3β/β-catenin signaling pathway plays a vital role in ischemic preconditioning. The present study attempts to evaluate whether PI3K/GSK-3β/β-catenin signaling pathway might be responsible for the cardioprotection in ischemic postconditioning. Male Sprague-Dawley rats underwent 30 min of left anterior descending coronary artery occlusion and 2 h of reperfusion. One hundred twenty rats were randomized into six groups: sham, ischemia/reperfusion (I/R), ischemic postconditioning (Post), 15 μg · kg wortmannin (PI3K inhibitor) plus ischemic postconditioning (Wort + Post), wortmannin plus I/R (Wort + I/R), and 0.6 mg · kg SB216763 (GSK-3β inhibitor) plus I/R (SB + I/R). Wortmannin and SB216763 were administered, respectively, 10 and 5 min before reperfusion. Myocardial infarct size; number of apoptotic cardiomyocytes; total Akt, GSK-3β; phosphorylated Akt, GSK-3β; β-catenin in cytosol and nucleus; and Bcl-2 protein were assessed. It was found that Post and SB + I/R reduced infarct size (32.3% [SD, 2.8%], 32.7% [SD, 2.1%], vs. 53.4% [SD, 3.2%], respectively, P < 0.05) and apoptotic index of cardiomyocytes (23.2% [SD, 1.8%], 23.8% [SD, 1.8%], vs. 47.3% [SD, 5.8%], respectively, P < 0.05); compared with I/R, wortmannin abolished the cardioprotection of ischemic postconditioning. Post and SB + I/R increased phosphorylated Akt, phosphorylated GSK3β, β-catenin in cytosol and nucleus, and Bcl-2 expression versus I/R. These results indicate that ischemic postconditioning could induce myocardial protection via PI3K/GSK-3β/β-catenin signaling pathway, activation of which results in accumulation of β-catenin and upregulation of its target genes Bcl-2.
authors.affiliation: Anesthesiology Department, the First Hospital Affiliated at China Medical University, Shenyang, China.
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Wu
authors.forename: Tu
authors.initials: T
authors.lastname: Shen
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shao
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Jun-Ke
authors.initials: JK
authors.lastname: Wang
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007211:Indoles / Q000494:pharmacology; D057775:Ischemic Postconditioning / Q000379:methods*; D008026:Ligation; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D000077191:Wortmannin; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000730:Androstadienes; D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; C417521:SB 216763; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D000077191:Wortmannin