The role of RIP3 in cardiomyocyte necrosis induced by mitochondrial damage of myocardial ischemia-reperfusion  

作　　者：Huifang Hou Yongling Wang Qiong Li Zaibing Li Yan Teng Jingyu Li Xiaoying Wang Junli Chen Ning Huang 

机构地区：[1]Department of Pathophysiology,West China School of Basic Medical Sciences and Forensic Medicine,Sichuan University,Chengdu 610041,China [2]Department of Pathophysiology,Xinxiang Medical University,Xinxiang 453003, China [3]School of Nursing,Xinxiang Medical University,Xinxiang 453003,China

出　　处：《Acta Biochimica et Biophysica Sinica》2018年第11期1131-1140,共10页生物化学与生物物理学报（英文版）

基　　金：the grants from the National Natural Science Foundation of China (No.81300113);the National Undergraduate Innovation and Entrepreneurship Training Program (No.201710472004).

摘　　要：Myocardial damage caused by myocardial ischemia-reperfusion injury (MIRI)is difficult to be alleviated because cardiomyocyte necrosis is an irreversible and unregulated death form.Recently, necroptosis,a necrosis form caused by tumor necrosis factor-α (TNF-α)and Fas ligand (FasL),was found to be regulated by receptor interacting protein 3 (RIP3)and RIP3-receptor interacting protein 1 (RIP1)-mixed lineage kinase domain like protein (MLKL)pathway.But it is unclear whether they also play a regulatory role in MIRI-induced necroptosis.Our previous results showed that in rat MIRI,RIP3 could translocate and express highly in mitochondria.Therefore,it is important to explore proteins that interact with RIP3 which was translocated to mitochondria.The aim of this study was to explore the role of RIP3 in cardiomyocyte necrosis induced by mitochondrial damage of hypoxia/reoxygenation (H/R).Our results showed that H/R could cause RIP3-depended mitochondrial fragmentation and necrosis-based death;and RIP3-promoted H/R-induced necroptosis in H9c2 cells through increasing lactate dehydrogenase release and inhibiting cell viability.This process did not require RIP1 or MLKL but dynamin-related protein 1 (Drp1),which was related to Drpl activation,reactive oxygen species elevation,and △Ψm decline.This study provides novel insights into the role of RIP3 in cardiomyocyte injury during H/R.RIP3 may serve as a potential target for the treatment of MIRI.

关 键 词：RIP3 Drp1 CARDIOMYOCYTE NECROSIS MYOCARDIAL ISCHEMIA-REPERFUSION INJURY MITOCHONDRIAL damage 

分 类 号：Q[生物学]