Translocation of δPKC to mitochondria during cardiac reperfusion enhances superoxide anion production and induces loss in mitochondrial function
Translocation of δPKC to mitochondria during cardiac reperfusion enhances superoxide anion production and induces loss in mitochondrial function
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DOI：
10.1016/j.abb.2005.05.007
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发表时间：
2005-07-15
影响因子：
3.9
通讯作者：
Szweda, LI
中科院分区：
文献类型：
--
作者：
Churchill, EN;Szweda, LI
在某些氧化应激条件下，蛋白激酶C的δ亚型（δPKC）被激活，导致该激酶转位至线粒体，从而引起细胞色素c的释放和细胞凋亡的诱导。在当前的研究中，评估了心肌再灌注诱导的δPKC转位对线粒体功能的影响。从经历缺血（30分钟）随后再灌注（15分钟）的心脏中分离出的线粒体，其超氧阴离子（O₂⁻·）产生速率显著增加。这与再灌注最初5分钟内δPKC转位至线粒体有关。δPKC转位仅在再灌注期间发生，并且通过向完整心脏灌注H₂O₂可模拟该过程，这表明再灌注期间存在氧化还原依赖性激活。灌注一种对PKC的δ亚型特异的肽抑制剂（δV1 - 1），可显著降低再灌注诱导的线粒体O₂⁻·产生的增加。最后，长时间再灌注（120分钟）时明显出现的线粒体呼吸活性下降，可通过抑制δPKC转位而完全防止。因此，δPKC是一种胞质内对氧化还原敏感的分子，它在再灌注期间超氧阴离子产生的放大以及随后线粒体功能的下降中起重要作用。（c）2005爱思唯尔公司。保留所有权利。
Activation of the delta-isoform of protein kinase C (delta PKC) by certain conditions of oxidative stress results in translocation of the kinase to the mitochondria leading to release of cytochrome c and the induction of apoptosis. In the current study, the effects of myocardial reperfusion-induced delta PKC translocation on mitochondrial function were assessed. Mitochondria isolated from hearts that had undergone ischemia (30 min) followed by reperfusion (15 min) exhibited a significant increase in the rate of superoxide anion (O-2(-center dot)) generation. This was associated with the translocation of delta PKC to the mitochondria within the first 5 min of reperfusion. delta PKC translocation occurred exclusively during reperfusion and could be mimicked by infusion of intact hearts with H2O2 suggesting redox-dependent activation during reperfusion. Infusion of a peptide inhibitor (delta V1-1) specific to the delta-isoform of PKC significantly reduced reperfusion-induced increases in mitochondrial O-2(-center dot) generation. Finally, the decline in mitochondrial respiratory activity evident upon prolonged reperfusion (120 min) was completely prevented by inhibition of delta PKC translocation. Thus, delta PKC represents a cytosolic redox-sensitive molecule that plays an important role in amplification of O-2(-center dot) production and subsequent declines in mitochondrial function during reperfusion, (c) 2005 Elsevier Inc. All rights reserved.