Biphasic modulation of the mitochondrial electron transport chain in myocardial ischemia and reperfusion
Biphasic modulation of the mitochondrial electron transport chain in myocardial ischemia and reperfusion
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DOI：
10.1152/ajpheart.00731.2011
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发表时间：
2012-04-01
影响因子：
4.8
通讯作者：
Chen, Yeong-Renn
中科院分区：
文献类型：
--
作者：
Lee, Hsin-Ling;Chen, Chwen-Lih;Chen, Yeong-Renn
李浩华，陈庆良，叶圣，蔡伟杰，陈耀荣。心肌缺血和再灌注时线粒体电子传递链的双相调节。Am J Physiol Heart Circ Physiol 302：H1410-H1422，2012。首次发表于2012年1月20日; doi：10.1152/ajpheart.00731.2011。线粒体电子传递链（ETC）是心肌缺血再灌注（I/R）损伤时活性氧的主要来源。缺血性缺损和再灌注损伤是缺血后心脏疾病发生的关键。在离体心脏模型中研究了ETC的性质。大鼠心脏缺血30 min，再灌注1 h。线粒体功能的研究表明，在I/R过程中，电子传递活性（ETA）和ETC蛋白表达的双相调节。在分离的线粒体中的ETA的分析表明，复合物I，II，III和IV的活动减少后30分钟的缺血，但增加后恢复流量。免疫印迹分析和透射电子显微镜超微结构分析进一步揭示了ETC在缺血心脏中的显著下调，然后再灌注时ETC上调。ETC的mRNA表达水平在缺血组和缺血后组间无显著性差异。然而，再灌注诱导的心肌ETC生物合成可以被放线菌酮抑制，表明参与翻译控制。组织匀浆的免疫印迹分析揭示了过氧化物酶体增殖物激活受体-γ共激活因子-1 α表达的相似特征，表明其作为I/R期间控制ETC生物合成的上游调节因子的重要作用。在复合物I-III中观察到由缺血和缺血后损伤引起的显著损害。NADH铁氰化物还原酶活性分析表明，黄素蛋白亚复合物的损伤占缺血心脏完整复合物I活性下降的50%。综上所述，我们的研究结果为I/R诱导的线粒体功能障碍的分子机制提供了新的见解。
Lee HL, Chen CL, Yeh ST, Zweier JL, Chen YR. Biphasic modulation of the mitochondrial electron transport chain in myocardial ischemia and reperfusion. Am J Physiol Heart Circ Physiol 302: H1410-H1422, 2012. First published January 20, 2012; doi: 10.1152/ajpheart.00731.2011.-Mitochondrial electron transport chain (ETC) is the major source of reactive oxygen species during myocardial ischemia-reperfusion (I/R) injury. Ischemic defect and reperfusion-induced injury to ETC are critical in the disease pathogenesis of postischemic heart. The properties of ETC were investigated in an isolated heart model of global I/R. Rat hearts were subjected to ischemia for 30 min followed by reperfusion for 1 h. Studies of mitochondrial function indicated a biphasic modulation of electron transfer activity (ETA) and ETC protein expression during I/R. Analysis of ETAs in the isolated mitochondria indicated that complexes I, II, III, and IV activities were diminished after 30 min of ischemia but increased upon restoration of flow. Immunoblotting analysis and ultrastructural analysis with transmission electron microscopy further revealed marked downregulation of ETC in the ischemic heart and then upregulation of ETC upon reperfusion. No significant difference in the mRNA expression level of ETC was detected between ischemic and postischemic hearts. However, reperfusion-induced ETC biosynthesis in myocardium can be inhibited by cycloheximide, indicating the involvement of translational control. Immunoblotting analysis of tissue homogenates revealed a similar profile in peroxisome proliferator-activated receptor-gamma coactivator-1 alpha expression, suggesting its essential role as an upstream regulator in controlling ETC biosynthesis during I/R. Significant impairment caused by ischemic and postischemic injury was observed in the complexes I-III. Analysis of NADH ferricyanide reductase activity indicated that injury of flavoprotein subcomplex accounts for 50% decline of intact complex I activity from ischemic heart. Taken together, our findings provide a new insight into the molecular mechanism of I/R-induced mitochondrial dysfunction.