Ischemic preconditioning protects cardiomyocytes against ischemic injury by inducing GRP78
Ischemic preconditioning protects cardiomyocytes against ischemic injury by inducing GRP78
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DOI：
10.1016/j.bbrc.2006.05.077
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发表时间：
2006-07-14
影响因子：
3.1
通讯作者：
Yoshida, Ken-ichi
中科院分区：
文献类型：
--
作者：
Shintani-Ishida, Kaori;Nakajima, Makoto;Yoshida, Ken-ichi
短暂性缺血再灌注诱导的缺血预适应(IP)可抵抗随后发生的致死性缺血所致的细胞损伤。本研究旨在阐明内质网主要分子伴侣78-kDa葡萄糖调节蛋白(GRP78)是否参与IP介导的抗心肌缺血损伤。在大鼠冠状动脉闭塞模型中，早期缺血4分钟和再灌流4分钟，GRP78蛋白水平增加到假手术水平的210%。在随后的致命性缺血中，IP减少了脑梗塞的范围。在原代培养的心肌细胞中，模拟的IP程序，即在缺氧-葡萄糖剥夺(OGD)介质中孵育，也增加了GRP78的表达，并抑制了致死性缺血所致的细胞死亡。GRP78反义寡核苷酸可减轻IP介导的缺血抵抗。这项研究首次表明，早期IP可上调心肌GRP78。提示早期缺血诱导的GRP78对心肌细胞的缺血损伤具有保护作用。(C)2006 Elsevier Inc.保留所有权利。
Ischemic preconditioning (IP) conferred by brief ischemia-reperfusion induces resistance to cell injury due to the following lethal ischemia. This study aimed to elucidate whether 78-kDa glucose-regulated protein (GRP78), a main ER molecular chaperone, contributes to IP-mediated protection against ischemic myocardial injury. In a rat coronary artery occlusion model, the GRP78 protein level increased to 210% of the sham level by early IP with three cycles of 4-min ischemia and 4-min reperfusion. The IP reduced infarct size in subsequent lethal ischemia. In primary cardiomyocytes, the simulated IP procedure, incubation in oxygen-glucose deprivation (OGD) medium, also increased the GRP78 expression and suppressed the cell death caused by lethal ischemia. Transfection of grp78 antisense oligonucleotide attenuated the IP-mediated resistance to ischemia. This study showed for the first time that early IP up-regulates myocardial GRP78. It was suggested that GRP78 induced by early IP contributes to protect cardiomyocytes against ischemic injury. (c) 2006 Elsevier Inc. All rights reserved.