Ischemic preconditioning or p38 MAP kinase inhibition attenuates myocardial TNF α production and mitochondria damage in brief myocardial ischemia
Ischemic preconditioning or p38 MAP kinase inhibition attenuates myocardial TNF α production and mitochondria damage in brief myocardial ischemia
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DOI：
10.1016/j.lfs.2005.08.040
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发表时间：
2006-03-20
期刊：
影响因子：
6.1
通讯作者：
Yoshida, K
中科院分区：
文献类型：
--
作者：
Kimura, H;Shintani-Ishida, K;Yoshida, K
冠状动脉结扎可使大鼠心脏细胞膜部分的肿瘤坏死因子α水平升高，在30min时几乎达到最大。在心肌缺血时，肿瘤坏死因子是一种免疫荧光标记的心肌细胞内的条纹状网状结构，而不是血管或间质细胞。免疫电子显微镜证实，肿瘤坏死因子α定位于肌原纤维、线粒体之间。或缺血心肌细胞中的其他膜结构。缺血预适应(IP)是对短暂的缺血-再灌注循环所产生的心肌保护作用。IP或p38MAPK抑制剂可抑制缺血后肿瘤坏死因子α产生的增加以及p38MAPK和S6蛋白的磷酸化(S]3203580，FR167653)。核糖体S6的磷酸化可能在转录后阶段调节肿瘤坏死因子α的产生，因为IP不抑制肿瘤坏死因子αmRNA的上调，并且不依赖于核糖体KappaB的激活。电子显微镜(EM)显示缺血心肌细胞线粒体损伤，IP或SB203580均可抑制这种损伤。这是首次证实缺血心肌细胞膜结构中的肿瘤坏死因子α上调是通过p38蛋白激酶介导的转录后机制，与线粒体损伤有关。(C)2005年，爱思唯尔公司出版。
Coronary artery occlusion increased the TNF alpha level in the membrane fraction of the rat heart, almost maximally at 30 min. TNF a immunofluorescence labeled streak-like reticular structures inside of the cardiomyocyte but not vascular or interstitial cells in myocardial ischemia. Immuno-electron microscopy confirmed the localization of TNF alpha between myofibrils, mitochondria. or other membrane structures in the ischemic cardiomyocyte. Ischemic preconditioning (IP) is the protection of myocardium conferred by cycles of brief ischemia-reperfusion. The increases in TNF alpha production, as well as phosphorylation of p38 MAP kinase and S6 kinase after ischemia were inhibited by IP or p38 MAP kinase inhibitors (S]3203580, FR167653). TNF a production appeared to be regulated possibly at the post-transcriptional step by ribosomal S6 phosphorylation given that IP did not suppress TNF alpha mRNA up-regulation and was independent of NF kappa B activation. Electron microscopy (EM) showed mitochondria damage in ischemic cardiomyocyte, which was inhibited either by IP or SB203580. This is the first demonstration of the TNF alpha up-regulation in membrane structures of ischemic cardiomyocyte through p38 MAP kinase-mediated post-transcriptional mechanism, in association with mitochondrial damage. (c) 2005 Published by Elsevier Inc.