Ischemic preconditioning activates AMPK in a PKC-dependent manner and induces GLUT4 up-regulation in the late phase of cardioprotection
Ischemic preconditioning activates AMPK in a PKC-dependent manner and induces GLUT4 up-regulation in the late phase of cardioprotection
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DOI：
10.1016/j.cardiores.2003.10.022
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发表时间：
2004-02-15
影响因子：
10.8
通讯作者：
Shimamoto, K
中科院分区：
文献类型：
--
作者：
Nishino, Y;Miura, T;Shimamoto, K
目的：本研究的目的是确定AMP激活的蛋白激酶（AMPK）在缺血预处理（PC）对抗心肌顿抑所提供的心脏保护晚期中的作用及其与蛋白激酶C（PKC）的联系。方法和结果：在家兔冠状动脉周围植入球囊封堵器，并使用多普勒传感器监测增厚分数（TF）。清醒家兔连续2天（第1天和第2天）进行5个周期的5分钟缺血/5分钟再灌注（I/R）。I/R后TF的减少明显较少，第2天TF的恢复更快，表明晚期PC效应。PC引起PKC-AMPK从胞浆到膜的易位，并在PC后立即使AMPK活性显著增加100%。葡萄糖转运蛋白GLUT 4的mRNA水平在PC后3 h增加了150%，GLUT 4的总蛋白水平在PC后24 h增加了107%。I/R后第2天的肌膜GLUT 4蛋白水平比I/R后第1天的肌膜GLUT 4蛋白水平高41%。通过用PKC抑制剂预处理，PC对AMPK激活和GLUT 4的上调被废除。结论：PC以PKC依赖的方式激活AMPK并上调GLUT 4的表达。这种GLUT 4在PC后24 h的上调可能有助于减轻心肌顿抑。(C)2003年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: The aim of this study was to determine the role of AMP-activated protein kinase (AMPK) and its link to protein kinase C (PKC) in the late phase of cardioprotection afforded by ischemic preconditioning (PC) against myocardial stunning. Methods and results: Rabbits were instrumented with a balloon occluder around a coronary artery and with a Doppler sensor to monitor the thickening fraction (TF). Conscious rabbits underwent five cycles of 5-min ischemia/5-min reperfusion (I/R) on 2 consecutive days (days I and 2). Reduction of TF after I/R was significantly less and recovery of TF was faster on day 2, indicating a late PC effect. PC provoked translocation of PKC-epsilon from the cytosol to the membrane and significantly increased AMPK activity by 100% immediately after PC. The mRNA level of GLUT4, a glucose transporter, was elevated by 150% at 3 h after PC, and the total protein level of GLUT4 was increased by 107% at 24 h after PC. The level of sarcolemmal GLUT4 protein after I/R on day 2 was 41% higher than its level after l/R on day 1. AMPK activation and up-regulation of GLUT4 by PC were abrogated by pre-treatment with PKC inhibitors. Conclusion: PC activated AMPK and up-regulated GLUT4 expression in a PKC-dependent manner. This GLUT4 up-regulation at 24 h after PC may contribute to attenuation of myocardial stunning. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.