Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice.
Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice.
复制标题
白藜芦醇对小鼠心脏的保护作用需要含有 Kir6.2 的 ATP 敏感 K 通道
DOI：
10.1186/1475-2840-13-35
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发表时间：
2014-02-05
影响因子：
9.3
通讯作者：
Hu G
中科院分区：
文献类型：
--
作者：
Du RH;Dai T;Cao WJ;Lu M;Ding JH;Hu G
背景：白藜芦醇是一种影响能量代谢的天然化合物，也被认为具有一系列心脏保护作用。然而，其对能量代谢的总体影响和心脏保护的潜在机制需要进一步研究。方法：建立Kir6.2基因敲除、Kir6.1杂合子和野生型小鼠心肌缺血再灌注损伤模型，腹腔注射白藜芦醇（10 mg/kg）。测定心肌梗死面积、血清乳酸脱氢酶（LDH）和肌酸激酶（CK）活性。结果：白藜芦醇能显著减少WT和Kir6.1杂合子小鼠心肌梗死面积，降低血清LDH和CK活性，抑制氧糖剥夺/复氧诱导的心肌细胞凋亡，但Kir6.2缺陷可取消白藜芦醇的心肌保护作用。我们进一步发现，白藜芦醇增强5 '-AMP-活化蛋白激酶（AMPK）的磷酸化，并促进AMPK与Kir6.2的缔合。AMPK的抑制减弱和AMPK的激活模拟了白藜芦醇在心肌细胞中的心脏保护作用。结论：白藜芦醇通过AMPK-Kir 6. 2/K-ATP信号通路发挥心肌保护作用，Kir6.2通道参与白藜芦醇的心肌保护作用。
Background:Resveratrol 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.Methods:Kir6.2 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.Results:Resveratrol 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.Conclusions:Our 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.
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影响因子：
9.3
作者：
Chen ZC;Cheng YZ;Chen LJ;Cheng KC;Li Y;Cheng J
通讯作者：
Cheng J
DOI：
10.1152/ajpheart.00348.2001
发表时间：
2002-04-01
影响因子：
4.8
作者：
Liu, HP;Zhang, HY;Yao, ZH
通讯作者：
Yao, ZH
影响因子：
6.6
作者：
Goh, Siew Simg C.;Woodman, Owen L.;Ritchie, Rebecca H.
通讯作者：
Ritchie, Rebecca H.
影响因子：
5.6
作者：
Sukhodub, Andrey;Jovanovic, Sofija;Du, Qingyou;Budas, Grant;Clelland, Allyson K;Shen, Mei;Sakamoto, Kei;Tian, Rong;Jovanovic, Aleksandar
通讯作者：
Jovanovic, Aleksandar
DOI：
10.1152/ajpheart.01048.2007
发表时间：
2008-02-01
影响因子：
4.8
作者：
Lekli, Istvan;Szabo, Gergo;Tosaki, Arpad
通讯作者：
Tosaki, Arpad