Chemical screening links disulfiram with cardiac protection after ischemic injury  

作　　者：Yuanyuan Chen Jianyong Du Lixia Zheng Zihao Wang Zongwang Zhang Zhengyuan Wu Xiaojun Zhu Jing-Wei Xiong 

机构地区：[1]Beijing Key Laboratory of Cardiometabolic Molecular Medicine,Institute of Molecular Medicine,College of Future Technology,and State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing 100871,China [2]School of Health and Life Sciences,University of Health and Rehabilitation Sciences,Qingdao 266071,China [3]PKU-Nanjing Institute of Translational Medicine,Nanjing 211800,China

出　　处：《Cell Regeneration》2023年第1期163-173,共11页细胞再生（英文）

基　　金：supported by grants from the National Key R&D Program of China(2018YFA0800501 and 2019YFA0801602);the National Natural Science Foundation of China(32230032,31730061,31430059,and 81870198);Shandong Provincial Natural Science Foundation(ZR2022QH394).

摘　　要：Ischemia-reperfusion injury occurs after reperfusion treatment for patients suffering myocardial infarction,however the underlying mechanisms are incompletely understood and effective pharmacological interventions are limited.Here,we report the identification and characterization of the FDA-approved drug disulfiram(DSF)as a cardioprotective compound.By applying high-throughput chemical screening,we found that DSF decreased H_(2)O_(2)-induced cardiomyocyte death by inhibiting Gasdermin D,but not ALDH1,in cardiomyocytes.Oral gavage of DSF decreased myocardial infarct size and improved heart function after myocardial ischemia-reperfusion injury in rats.Therefore,this work reveals DSF as a potential therapeutic compound for the treatment of ischemic heart disease.

关 键 词：Small molecule High-throughput chemical screening DISULFIRAM Gasdermin D Ischemia/reperfusion injury Rat cardiomyocytes 

分 类 号：R541[医药卫生—心血管疾病]