DJ-1 protects the heart against ischemia-reperfusion injury by regulating mitochondrial fission.
DJ-1 protects the heart against ischemia-reperfusion injury by regulating mitochondrial fission.
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DOI：
10.1016/j.yjmcc.2016.04.008
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发表时间：
2016-08
影响因子：
5
通讯作者：
Calvert, John W.
中科院分区：
文献类型：
--
作者：
Shimizu, Yuuki;Lambert, Jonathan P.;Nicholson, Chad K.;Kim, Joshua J.;Wolfson, David W.;Cho, Hee Cheol;Husain, Ahsan;Naqvi, Nawazish;Chin, Li-Shen;Li, Lian;Calvert, John W.
最近的数据表明DJ-1在细胞对压力的反应中起作用。在这里，我们的目的是研究潜在的分子机制介导的DJ-1在心脏缺血再灌注（I/R）损伤后的行动。响应于I/R损伤，与WT小鼠相比，DJ-1 KO小鼠显示出梗死面积增加和左心室功能恶化，证实了DJ-1在心脏中的保护作用。为了评估DJ-1 KO小鼠损伤增加的潜在机制，我们重点研究了SUMO化，这是一种调节蛋白质功能各个方面的翻译后修饰过程。发现I/R损伤后的DJ-1 KO心脏显示SUMO-1修饰蛋白的积累增加和SUMO-2/3修饰蛋白的减少。进一步的分析显示，在I/R损伤后DJ-1 KO心脏中，去SUMO化酶SENP 1的蛋白表达降低，而SENP 5的表达增强。最后，发现DJ-1 KO心脏显示出动力蛋白相关蛋白1的SUMO-1修饰增强、线粒体过度分裂和线粒体功能障碍。我们的数据表明，DJ-1在心肌I/R损伤中的激活通过调节Drp 1的SUMO化状态和减弱过度的线粒体分裂来保护心脏。
Recent data indicates that DJ-1 plays a role in the cellular response to stress. Here, we aimed to examine the underlying molecular mechanisms mediating the actions of DJ-1 in the heart following myocardial ischemia-reperfusion (I/R) injury. In response to I/R injury, DJ-1 KO mice displayed increased areas of infarction and worsened left ventricular function when compared to WT mice, confirming a protective role for DJ-1 in the heart. In an effort to evaluate the potential mechanism(s) responsible for the increased injury in DJ-1 KO mice, we focused on SUMOylation, a post-translational modification process that regulates various aspects of protein function. DJ-1 KO hearts after I/R injury were found to display enhanced accumulation of SUMO-1 modified proteins and reduced SUMO-2/3 modified proteins. Further analysis, revealed that the protein expression of the de-SUMOylation enzyme SENP1 was reduced, whereas the expression of SENP5 was enhanced in DJ-1 KO hearts after I/R injury. Finally, DJ-1 KO hearts were found to display enhanced SUMO-1 modification of dynamin-related protein 1, excessive mitochondrial fission, and dysfunctional mitochondria. Our data demonstrates that the activation of DJ-1 in response to myocardial I/R injury protects the heart by regulating the SUMOylation status of Drp1 and attenuating excessive mitochondrial fission.
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影响因子：
46.9
作者：
通讯作者：
--
影响因子：
5
作者：
Nicholson, Chad K.;Lambert, Jonathan P.;Chow, Chi-Wing;Lefer, David J.;Calvert, John W.
通讯作者：
Calvert, John W.
DOI：
10.1073/pnas.1213294110
发表时间：
2013-04-09
影响因子：
11.1
作者：
Din, Shabana;Mason, Matthew;Sussman, Mark A.
通讯作者：
Sussman, Mark A.
影响因子：
4.8
作者：
Figueroa-Romero, Claudia;Iniguez-Lluhi, Jorge A.;Feldman, Eva L.
通讯作者：
Feldman, Eva L.
影响因子：
7
作者：
Rosas-Acosta, G;Russell, WK;Wilson, VG
通讯作者：
Wilson, VG