ZYZ451 Protects cardiomyocytes from hypoxia-induced apoptosis by enhancing MnSOD and STAT3 interaction

作     者：Shan-shan LUO Ya-qi SHEN Li-ming MA Xian-feng GU Yi-zhun ZHU 

作者机构：Department of Pharmacology School of Pharmacy Fudan University Shanghai 201203 China Department of Medicinal Chemistry School of Pharmacy Fudan University Shanghai 201203 China Department of Pharmacology Loo Yong Lin School of Medicine National University of Singapore Singapore 

出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)

年 卷 期：2015年第29卷第S1期

页      面：27-28页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：The project supported by National Natural Science Foundation of China(81330080) Key laboratory program of the Education Commission of Shanghai Municipality(ZDSYS14005) Shanghai Committee of Science and Technology(14JC1401100) 

主　　题：hypoxia acute myocardial infarction ROS MnSOD apop 

摘      要：OBJECTIVE 3,5-Dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester(ZYZ451)showed excellent cardio-protective effects in our previous ***,its therapeutic potential in vivo and the mechanism remained to be ***,we evaluated cardiac protective role of ZYZ451 in post-myocardial infarction(post-MI)rats,and elucidated the underlying *** Neonatal rat ventricular cardiomyoctys(NRVCs)were separated and subjected to pre-deoxidized(1%O2,5%CO2),and serum-free medium for 4h to obtain ischemic *** ROS,MnSOD activity and cell apoptosis were tested to verify the cardiac protective effects of *** and siRNA for Stat3 were used to determine role of Stat3 played in cardio-protective effectes of *** were isolated from NRVCs to determine expression of Stat3 and *** and coimmunoprecipitation were conducted to determine the interaction between MnSOD and *** apply post-MI model in rats,the rats were subjected to ligation of LAD except for control *** vehicle or ZYZ451(1,2or 5mg·kg-1)or mixture of Leonurine and SPRC(15mg·kg-1)was administered 7dbefore and 3more days after the *** at risk(AAR),apoptosis in AAR,LDH and MDA levels,and MnSOD activity and expression were detected to evaluate the cardiac *** mitochondria were isolated to determine MnSOD and Stat3 expression in ischemia,and coimmunoprecipitaion was performed to verify the interaction between MnSOD and Stat3 in *** ZYZ451 prevented hypoxia induced NRVCs apoptosis via increasing MnSOD activity and inhibiting mitochondrial ROS ***,5,15-DPP(STAT3phosphorylation inhibitor)failed to inhibit MnSOD activity,while knockout of STAT3 resulted in significant reduction of MnSOD activity,followed by increased mitochondrial ROS production and cardiomyocytes apoptosis in ***,protective effects of ZYZ451 were blunted in Stat3 deficient