Soluble epoxide hydrolase activation by S-nitrosation contributes to cardiac ischemia-reperfusion injury
Ding, Yuzhu3; Li, Yazi2; Zhang, Xu5; He, Jinlong5; Lu, Dong4; Fang, Xuan3; Wang, Yuchen3; Wang, Jiaxing3; Zhang, Yuying2; Qiao, Xinhua2
刊名JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
2017-09
卷号110页码:70-79
关键词Epoxyeicosatrienoic acid Ischemia-reperfusion Nitric oxide S-nitrosation Soluble epoxide hydrolase
ISSN号0022-2828
DOI10.1016/j.yjmcc.2017.07.006
文献子类Article
英文摘要Cardiac ischemia-reperfusion (I/R) injury always accompanies recanalization treatment for myocardial infarction. Here we found soluble epoxide hydrolase (sEH), which metabolizes cardioprotective epoxyeicosatrienoic acids into less effective diols, was rapidly activated during myocardial reperfusion in both mouse and rat models in expression-independent manner. Similar activation was mimicked by nitric oxide (NO) donor dose-dependently in vitro, along with an obvious induction of sEH S-nitrosation, a short-term post-translational modification, which diminished in sEH Cys-141-Ala mutant. In vivo, I/R induced sEH S-nitrosation could be reversed by NO synthase inhibitor L-NAME, with protective effect on cardiac dysfunction, which however vanished in sEH(-/-) mice. Further, a protective effect against I/R injury in the initial phase of reperfusion was observed in eNOS(-/-) mice, indicating inhibition of NO as a sEH-based cardioprotective in early time of I/R injury. Besides, sEH inhibitor directly targeting on activated sEH during cardiac reperfusion significant reduced infarct size after I/R in vivo. In summary, our findings show the critical role of sEH S-nitrosation in cardiac I/R injury and inhibiting sEH S-nitrosation may be a new therapeutic strategy clinically. (C) 2017 Elsevier Ltd. All rights reserved.
资助项目Ministry of Science and Technology of China[2016YFC0903000] ; Ministry of Science and Technology of China[2015BAI08B01] ; National Natural Science Foundation of China[81420108003] ; National Natural Science Foundation of China[31225012] ; National Natural Science Foundation of China[81400320] ; National Natural Science Foundation of China[91539108] ; Peking University-AstraZeneca Collaborative grant[SEML-89HH3C]
WOS关键词ENDOTHELIUM IN-VITRO ; EPOXYEICOSATRIENOIC ACIDS ; ARACHIDONIC-ACID ; INFARCT SIZE ; NITROSYLATION ; RATS ; INHIBITION ; MECHANISM ; HEART ; VIVO
WOS研究方向Cardiovascular System & Cardiology ; Cell Biology
语种英语
出版者ELSEVIER SCI LTD
WOS记录号WOS:000411422500008
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/272496]  
专题药物发现与设计中心
通讯作者Chen, Chang; Zhu, Yi
作者单位1.AstraZeneca R&D, Innovat Med & Early Dev, SE-43183 Molndal, Sweden
2.Chinese Acad Sci, Natl Lab Biomacromol, Inst Biophys, Beijing 100101, Peoples R China;
3.Peking Univ, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Beijing 100191, Peoples R China;
4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
5.Tianjin Med Univ, Tianjin Key Lab Metab Dis, Collaborat Innovat Ctr Tianjin Med Epigenet, Dept Physiol & Pathophysiol, Tianjin 300070, Peoples R China;
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Ding, Yuzhu,Li, Yazi,Zhang, Xu,et al. Soluble epoxide hydrolase activation by S-nitrosation contributes to cardiac ischemia-reperfusion injury[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2017,110:70-79.
APA Ding, Yuzhu.,Li, Yazi.,Zhang, Xu.,He, Jinlong.,Lu, Dong.,...&Zhu, Yi.(2017).Soluble epoxide hydrolase activation by S-nitrosation contributes to cardiac ischemia-reperfusion injury.JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,110,70-79.
MLA Ding, Yuzhu,et al."Soluble epoxide hydrolase activation by S-nitrosation contributes to cardiac ischemia-reperfusion injury".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 110(2017):70-79.
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