Background: SIRT1, which belongs to the Sirtuin family of NAD-dependent enzymes, plays diverse roles in aging, metabolism, and disease biology. It could regulate cell survival and has been shown to be a protective factor in heart function. Hence, we verified the mechanism by which SIRT1 regulates doxorubicin induced cardiomyocyte injury in vivo and in vitro. Methods: We analyzed SIRT1 expression in doxorubicin-induced neonatal rat cardiomyocyte injury model and adult mouse heart failure model. SIRT1 was over-expressed in cultured neonatal rat cardiomyocyte by adenovirus mediated gene transfer. SIRT1 agonist resveratrol was used to treat the doxorubicin-induced heart failure mouse model. Echocardiography, reactive oxygen species (ROS) production, TUNEL, qRT-PCR, and Western blotting were performed to analyze cell survival, oxidative stress, and inflammatory signal pathways in cardiomyocytes. Results: SIRT1 expression was down-regulated in doxorubicin induced cardiomocyte injury, accompanied by elevated oxidative stress and cell apoptosis. SIRT1 over-expression reduced doxorubicin induced cardiomyocyte apoptosis with the attenuated ROS production. SIRT1 also reduced cell apoptosis by inhibition of p38MAPK phosphorylation and caspase-3 activation. The SIRT1 agonist resveratrol was able to prevent doxorubicin-induced heart function loss. Moreover, the SIRT1 inhibitor niacinamide could reverse SIRT1's protective effect in cultured neonatal rat cardiomyocytes. Conclusions: These results support the role of SIRT1 as an important regulator of cardiomyocyte apoptosis during doxorubicin-induced heart injury, which may represent a potential therapeutic target for doxorubicin-induced cardiomyopathy. Copyright (C) 2015 S. Karger AG, Basel
基金：
National Basic Research Program of ChinaNational Basic Research Program of China [2012CB517502, 2014CB910503]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81470427, 81200221, 81270887]; Beijing Natural Science FoundationBeijing Natural Science Foundation [7142142]
第一作者机构：[1]Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China;[2]Beijing Inst Heart Lung & Blood Vessel Dis, Beijing 100730, Peoples R China;
通讯作者：
通讯机构：[7]Minist Hlth China, Key Lab Geriatr, Beijing, Peoples R China;[8]Minist Hlth China, Beijing Hosp, Beijing, Peoples R China;[9]Minist Hlth China, Beijing Inst Geriatr, Beijing, Peoples R China;[10]Beijing Hosp, Key Lab Geriatr, Room 11-2 11th Floor Phys Examinat Bldg, Beijing 100730, Peoples R China
推荐引用方式(GB/T 7714)：
Ruan Yang,Dong Chunlin,Patel Jigar,et al.SIRT1 Suppresses Doxorubicin-Induced Cardiotoxicity by Regulating the Oxidative Stress and p38MAPK Pathways[J].CELLULAR PHYSIOLOGY AND BIOCHEMISTRY.2015,35(3):1116-1124.doi:10.1159/000373937.
APA：
Ruan, Yang,Dong, Chunlin,Patel, Jigar,Duan, Chao,Wang, Xinyue...&Li, Jian.(2015).SIRT1 Suppresses Doxorubicin-Induced Cardiotoxicity by Regulating the Oxidative Stress and p38MAPK Pathways.CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,35,(3)
MLA：
Ruan, Yang,et al."SIRT1 Suppresses Doxorubicin-Induced Cardiotoxicity by Regulating the Oxidative Stress and p38MAPK Pathways".CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 35..3(2015):1116-1124
