Interleukin 35 protects cardiomyocytes following ischemia/reperfusion-induced apoptosis via activation of mitochondrial STAT3  

作　　者：Fengyun Zhou Ting Feng Xiangqi Lu Huicheng Wang Yangping Chen Qiuxia Zhang Xinlu Zhang Jiancheng Xiu 

机构地区：[1]Department of Cardiology,State Key Laboratory of Organ Failure Research,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第4期410-418,共9页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.81974266,81470598,and 81800371);the National Key R&D Program of China(No.2018 YFC1312803).

摘　　要：Mitochondrial reactive oxygen species(mtROS)-induced apoptosis has been suggested to contribute to myocardial ischemia/reperfusion injury.Interleukin 35(IL-35),a novel anti-inflammatory cytokine,has been shown to protect the myocardium and inhibit mtROS production.However,its effect on cardiomyocytes upon exposure to hypoxia/reoxygenation(H/R)damage has not yet been elucidated.The present study aimed to investigate the potential protective role and underlying mechanisms of IL-35 in H/R-induced mouse neonatal cardiomyocyte injury.Mouse neonatal cardiomyocytes were challenged to H/R in the presence of IL-35,and we found that IL-35 dose dependently promotes cell viability,diminishes mtROS,maintains mitochondrial membrane potential,and decreases the number of apoptotic cardiomyocytes.Meanwhile,IL-35 remarkably activates mitochondrial STAT3(mitoSTAT3)signaling,inhibits cytochrome c release,and reduces apoptosis signaling.Furthermore,co-treatment of the cardiomyocytes with the STAT3 inhibitor AG490 abrogates the IL-35-induced cardioprotective effects.Our study identified the protective role of IL-35 in cardiomyocytes following H/R damage and revealed that IL-35 protects cardiomyocytes against mtROS-induced apoptosis through the mitoSTAT3 signaling pathway during H/R.

关 键 词：apoptosis HYPOXIA/REOXYGENATION IL-35 ROS STAT3 

分 类 号：R542.2[医药卫生—心血管疾病]