PIAS1 protects against myocardial ischemia-reperfusion injury by stimulating PPARγ SUMOylation.
PIAS1 protects against myocardial ischemia-reperfusion injury by stimulating PPARγ SUMOylation.
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DOI：
10.1186/s12860-018-0176-x
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发表时间：
2018-11-12
期刊：
影响因子：
--
通讯作者：
Xue S
中科院分区：
文献类型：
--
作者：
Xie B;Liu X;Yang J;Cheng J;Gu J;Xue S
心肌缺血再灌注损伤（IRI）已成为急性心肌梗死患者再灌注治疗后最严重的并发症之一。小泛素样修饰（SUMO化）是一个可逆过程，包括SUMO E1、E2和E3介导的SUMO化和SUMO特异性蛋白酶介导的去SUMO化，后者已被证明在心肌IRI中发挥重要作用。然而，人们对 SUMO E3 连接酶在心肌 IRI 中的功能和调节知之甚少。在这项研究中，我们发现小鼠心肌和 H9C2 细胞缺血/再灌注 (I/R) 后 PIAS1 的表达显着降低。 PIAS1 缺陷通过激活 I/R 后的 NF-κB 通路，加重心肌细胞的凋亡和炎症。从机制上讲，我们确定 PIAS1 是 PPARγ SUMO 化的特异性 E3 连接酶。此外，经缺氧/复氧（H/R）处理的H9C2细胞由于PIAS1下调而表现出PPARγ SUMO化减少，并通过抑制NF-κB活性发挥抗凋亡和抗炎功能。最后，H9C2 细胞中 PIAS1 的过度表达可以显着改善 I/R 损伤。总的来说，我们的研究结果证明了 PIAS1 介导的 PPARγ SUMO 化在预防心肌 IRI 中的关键作用。本文的在线版本 (10.1186/s12860-018-0176-x) 包含补充材料，可供授权用户使用。
Myocardial ischemia-reperfusion injury (IRI) has become one of the most serious complications after reperfusion therapy in patients with acute myocardial infarction. Small ubiquitin-like modification (SUMOylation) is a reversible process, including SUMO E1-, E2-, and E3-mediated SUMOylation and SUMO-specific protease-mediated deSUMOylation, with the latter having been shown to play a vital role in myocardial IRI previously. However, little is known about the function and regulation of SUMO E3 ligases in myocardial IRI. In this study, we found dramatically decreased expression of PIAS1 after ischemia/reperfusion (I/R) in mouse myocardium and H9C2 cells. PIAS1 deficiency aggravated apoptosis and inflammation of cardiomyocytes via activating the NF-κB pathway after I/R. Mechanistically, we identified PIAS1 as a specific E3 ligase for PPARγ SUMOylation. Moreover, H9C2 cells treated with hypoxia/reoxygenation (H/R) displayed reduced PPARγ SUMOylation as a result of down-regulated PIAS1, and act an anti-apoptotic and anti-inflammatory function through repressing NF-κB activity. Finally, overexpression of PIAS1 in H9C2 cells could remarkably ameliorate I/R injury. Collectively, our findings demonstrate the crucial role of PIAS1-mediated PPARγ SUMOylation in protecting against myocardial IRI. The online version of this article (10.1186/s12860-018-0176-x) contains supplementary material, which is available to authorized users.
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