ZYZ-803 Mitigates Endoplasmic Reticulum Stress-Related Necroptosis after Acute Myocardial Infarction through Downregulating the RIP3-CaMKII Signaling Pathway. (2nd June 2019)

• Record Type: Journal Article
• Authors: Chang, Lingling; Wang, Zhijun; Ma, Fenfen; Tran, Bahieu; Zhong, Rui; Xiong, Ying; Dai, Tao; Wu, Jian; Xin, Xiaoming; Guo, Wei; Xie, Ying; Mao, Yicheng; Zhu, Yi-Zhun
• Other Names: Sinha Mithun Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2019(2019)
• Publication Date: 2019-06-02
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2019/6173685
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide, and both cardiac necroptosis and endoplasmic reticulum stress (ERS) have been involved in the pathophysiology of AMI. ZYZ-803 is a hybrid molecule of a dual donor for gasotransmitters H2 S and NO. The aim of the present study is to investigate the antinecroptosis role and potential mechanisms of ZYZ-803 in the setting of ERS during AMI injury. In vivo, ZYZ-803 preserves cardiac function and reduces infarct size significantly after 24-hour left coronary artery ligation through revising H2 S and NO imbalance. In addition, ZYZ-803 relieves ERS and necroptosis in an AMI heart. In vitro, ZYZ-803 ameliorates ERS-related necroptosis induced by tunicamycin, and such effect has been depending on the receptor-interacting protein 3- (RIP3-) Ca 2+ -calmodulin-dependent protein kinase (CaMKII) signaling pathway. These findings have identified a novel antinecroptosis potential of ZYZ-803, providing a valuable candidate for cardioprotection in acute myocardial ischemia.