Aldehyde Dehydrogenase 2 Has Cardioprotective Effects on Myocardial Ischaemia/Reperfusion Injury via Suppressing Mitophagy.
Aldehyde Dehydrogenase 2 Has Cardioprotective Effects on Myocardial Ischaemia/Reperfusion Injury via Suppressing Mitophagy.
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DOI：
10.3389/fphar.2016.00101
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发表时间：
2016
影响因子：
5.6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Ji W;Wei S;Hao P;Xing J;Yuan Q;Wang J;Xu F;Chen Y
线粒体自噬是自噬的一种选择性形式，在心肌缺血/再灌注（I/R）中被过度激活。本研究探讨乙醛脱氢酶2（ALDH 2）是否通过调节线粒体自噬发挥其心脏保护作用。ALDH 2激活剂Alda-1可减轻大鼠I/R后心肌梗死面积和细胞凋亡，ALDH 2抑制剂可加重心肌梗死面积和细胞凋亡。在I/R大鼠和缺氧/复氧H9 C2细胞中，ALDH 2激活通过阻止4-羟基壬烯醛、活性氧和线粒体超氧化物积累来抑制磷酸酶和张力蛋白同源物诱导的推定激酶1（PINK 1）/Parkin表达，调节线粒体自噬。此外，ALDH 2抑制增强了该效果。因此，ALDH 2可能通过抑制PINK 1/Parkin依赖的线粒体自噬来保护心脏免受I/R损伤。
Mitophagy, a selective form of autophagy, is excessively activated in myocardial ischemia/reperfusion (I/R). The study investigated whether aldehyde dehydrogenase 2 (ALDH2) exerted its cardioprotective effect by regulating mitophagy. Myocardial infarct size and apoptosis after I/R in rats were ameliorated by Alda-1, an ALDH2 activator, and aggravated by ALDH2 inhibition. Both in I/R rats and hypoxia/reoxygenation H9C2 cells, ALDH2 activation suppressed phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/Parkin expression, regulating mitophagy, by preventing 4-hydroxynonenal, reactive oxygen species and mitochondrial superoxide accumulation. Furthermore, the effect was enhanced by ALDH2 inhibition. Thus, ALDH2 may protect hearts against I/R injury by suppressing PINK1/Parkin–dependent mitophagy.