Kir6.2-containing ATP-sensitive K+ channel is required for cardioprotection of resveratrol in mice

Cardiovascular Diabetology

Original Investigation

Ming Lu¹  Gang Hu¹  Wen-Jing Cao¹  Ren-Hong Du¹  Jian-hua Ding¹  Ting Dai¹ 

[1] Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, 210029, Nanjing, Jiangsu, P.R. China;

关键词: Resveratrol;    ATP-sensitive potassium channel;    Kir6.2;    Myocardial Ischemia/reperfusion;    5′-AMP-activated protein kinase;   

DOI  :  10.1186/1475-2840-13-35

 received in 2013-11-27, accepted in 2014-01-21,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundResveratrol is a natural compound that affects energy metabolism and is also known to possess an array of cardioprotective effects. However, its overall effects on energy metabolism and the underlying mechanism involved in cardioprotection require further investigation. Herein we hypothesize that ATP-sensitive potassium (K-ATP) channels as molecular sensors of cellular metabolism may mediate the cardioprotective effects of resveratrol.MethodsKir6.2 knockout, Kir6.1 heterozygous and wild-type (WT) mice were subjected to ischemia/reperfusion injury and were injected with resveratrol (10 mg/kg, i.p). Myocardial infarct size, serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities were determined. Neonatal cardiomyocytes were used in in vitro assays to investigate the underlying mechanism of resveratrol in cardioprotection.ResultsResveratrol treatment significantly reduced myocardial infarct size and serum LDH and CK activity and inhibited oxygen-glucose deprivation/reoxygenation – induced cardiomyocyte apoptosis in WT and Kir6.1 heterozygous mice, but Kir6.2 deficiency can abolish the cardioprotective effects of resveratrol in vivo and in vitro. We further found that resveratrol enhanced 5′-AMP-activated protein kinase (AMPK) phosphorylation and promoted the association of AMPK with Kir6.2. Suppression of AMPK attenuated and activation of AMPK mimicked the cardioprotective effects of resveratrol in cardiomyocytes. Notably, Kir6.2 knockout also reversed the cardioprotection of AMPK activator.ConclusionsOur study demonstrates that resveratrol exerts cardioprotective effects through AMPK -Kir6.2/K-ATP signal pathway and Kir6.2-containing K-ATP channel is required for cardioprotection of resveratrol.

【 授权许可】

Unknown   
© Du et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.