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ZYZ-803 Mitigates Endoplasmic Reticulum Stress-Related Necroptosis after Acute Myocardial Infarction through Downregulating the RIP3-CaMKII Signaling Pathway.

著者 Chang L , Wang Z , Ma F , Tran B , Zhong R , Xiong Y , Dai T , Wu J , Xin X , Guo W , Xie Y , Mao Y , Zhu YZ
Oxid Med Cell Longev.2019 ; 2019():6173685.
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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 HS 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. , ZYZ-803 preserves cardiac function and reduces infarct size significantly after 24-hour left coronary artery ligation through revising HS and NO imbalance. In addition, ZYZ-803 relieves ERS and necroptosis in an AMI heart. , ZYZ-803 ameliorates ERS-related necroptosis induced by tunicamycin, and such effect has been depending on the receptor-interacting protein 3- (RIP3-) Ca-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.
PMID: 31281585 [PubMed - in process]
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