Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu, PR China.
Xuzhou Medical University Affiliated Hospital, Xuzhou, Jiangsu, PR China.
J Mol Cell Cardiol. 2019 Sep;134:154-164. doi: 10.1016/j.yjmcc.2019.07.009. Epub 2019 Jul 22.
Myocardial ischemia/reperfusion (MI/R) injury has a great influence on the prognosis of patients with acute coronary occlusion. The underlying mechanisms of MI/R injury are complex. While the incidence of MI/R injury is increasing every year, the existing therapies are not satisfactory. Recently, small ubiquitin-related modifier (SUMO), which is a post-translational modification and involved in many cell processes, was found to play remarkable roles in MI/R injury. Several proteins that can be SUMOylated were found to interfere with different mechanisms of MI/R injury. Sarcoplasmic reticulum Ca ATPase pump SUMOylation alleviated calcium overload. Among the histone deacetylase (HDAC) members, SUMOylation of HDAC4 reduced reactive oxygen species generation, whereas Sirt1 played protective roles in the SUMOylated form. Dynamic-related protein 1 modified by different SUMO proteins exerted opposite effects on the function of mitochondria. SUMOylation of hypoxia-inducible factors was fundamental in oxygen homeostasis, while eukaryotic elongation factor 2 SUMOylation induced cardiomyocyte apoptosis. The impact of other SUMOylation substrates in MI/R injury remains unclear. Here we reviewed how these SUMOylated proteins alleviated or exacerbated myocardial impairments by effecting the MI/R injury mechanisms. This may suggest methods for relieving MI/R injury in clinical practice and provide a reference for further study of SUMOylation in MI/R injury.
心肌缺血/再灌注（MI/R）损伤对急性冠状动脉闭塞患者的预后有很大影响。MI/R 损伤的潜在机制很复杂。虽然 MI/R 损伤的发病率每年都在增加，但现有的治疗方法并不令人满意。最近，小泛素相关修饰物（SUMO）被发现对 MI/R 损伤起着显著作用，SUMO 是一种翻译后修饰物，参与许多细胞过程。有几种可以 SUMO 化的蛋白质被发现干扰了 MI/R 损伤的不同机制。肌浆网 Ca2+-ATP 酶泵 SUMO 化减轻了钙超载。在组蛋白去乙酰化酶（HDAC）成员中，HDAC4 的 SUMO 化减少了活性氧的产生，而 Sirt1 以 SUMO 化形式发挥保护作用。不同 SUMO 蛋白修饰的动力相关蛋白 1对线粒体的功能产生相反的影响。缺氧诱导因子的 SUMO 化对氧平衡至关重要，而真核延伸因子 2 SUMO 化诱导心肌细胞凋亡。其他 SUMO 化底物在 MI/R 损伤中的作用尚不清楚。在这里，我们综述了这些 SUMO 化蛋白如何通过影响 MI/R 损伤机制来减轻或加重心肌损伤。这可能为临床实践中缓解 MI/R 损伤提供方法，并为进一步研究 MI/R 损伤中的 SUMO 化提供参考。
