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Grb2-associated binder 1 is essential for cardioprotection against ischemia/reperfusion injury
Sun, Lulu1; Chen, Chao2,3; Jiang, Beibei1; Li, Yanli1; Deng, Qiuping1; Sun, Min2,3; An, Xiangbo2,3; Yang, Xiao4,5; Yang, Ying1; Zhang, Rongli1; Lu, Yao1; Zhu, De-Sheng6; Huo, Yingqing1; Feng, Gen-Sheng7; Zhang, Youyi2,3,8; Luo, Jincai1
关键词Gab1 Ischemia/reperfusion Injury Cardioprotection Cell Survival
刊名BASIC RESEARCH IN CARDIOLOGY
2014-06-21
DOI10.1007/s00395-014-0420-2
109期:4
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems
研究领域[WOS]Cardiovascular System & Cardiology
关键词[WOS]ISCHEMIA-REPERFUSION INJURY ; ACUTE MYOCARDIAL-INFARCTION ; CULTURED CARDIAC MYOCYTES ; ACTIVATED PROTEIN-KINASES ; CARDIOMYOCYTES IN-VITRO ; OXIDATIVE STRESS ; GROWTH-FACTOR ; SIGNAL-TRANSDUCTION ; CELL-SURVIVAL ; DOCKING PROTEIN
英文摘要

We have shown recently that endothelial Grb-2-associated binder 1 (Gab1), an intracellular scaffolding adaptor, has a protective effect against limb ischemia via mediating angiogenic signaling pathways. However, the role of Gab1 in cardiac ischemia/reperfusion (I/R) injury remains unknown. In this study, we show that Gab1 is required for cardioprotection against I/R injury. I/R injury led to remarkable phosphorylation of Gab1 in cardiomyocytes. Compared with controls, the mice with cardiomyocyte-specific deletion of Gab1 gene (CGKO mice) exhibited an increase in infarct size and a decrease in cardiac function after I/R injury. Consistently, in hearts of CGKO mice subjected to I/R, the activation of caspase 3 and myocardial apoptosis was markedly enhanced whereas the activation of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK), which are critical for cardiomyocyte survival, was attenuated. Oxidative stress is regarded as a major contributor to myocardial I/R injury. To examine the role of Gab1 in oxidative stress directly, isolated adult cardiomyocytes were subject to oxidant hydrogen peroxide and the cardioprotective effects of Gab1 were confirmed. Furthermore, we found that the phosphorylation of Gab1 and Gab1-mediated activation of Akt and MAPK by oxidative stress was suppressed by ErbB receptor and Src kinase inhibitors, accompanied by an increase in apoptotic cell death. In conclusion, our results suggest that Gab1 is essential for cardioprotection against I/R oxidative injury via mediating survival signaling.

语种英语
WOS记录号WOS:000338319800001
项目编号91339111 ; 81170098 ; 31221002 ; 2007CB512100 ; 5082009 ; 2011CB503903 ; 81030001 ; 30910103902 ; 2009ZX09501-027 ; NIHR01HL096125
资助机构National Science Foundation of China ; Major State Basic Research Development Programs of China ; Beijing Municipal Science Funds ; National Basic Research Program of China ; National Natural Science Foundation of China ; Projects for International Cooperation and Exchanges NSFC ; Key Project for Drug Discovery and Development in China ; National Institutes of Health Research Grant
引用统计
被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59825
专题北京大学第三临床医学院
北京大学第三临床医学院_医学工程处
北京大学精神卫生研究所_精神科
作者单位1.Peking Univ, Lab Vasc Biol, Inst Mol Med, Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China
2.Peking Univ, Hosp 3, Beijing 100871, Peoples R China
3.Minist Hlth, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing, Peoples R China
4.Inst Biotechnol, State Key Lab Prote, Beijing, Peoples R China
5.Genet Lab Dev & Dis, Beijing, Peoples R China
6.Peking Univ, Anim Ctr, Beijing 100871, Peoples R China
7.Univ Calif San Diego, Dept Pathol, Sch Med, San Diego, CA 92093 USA
8.Peking Univ, Inst Vasc Med, Hosp 3, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Sun, Lulu,Chen, Chao,Jiang, Beibei,et al. Grb2-associated binder 1 is essential for cardioprotection against ischemia/reperfusion injury[J]. BASIC RESEARCH IN CARDIOLOGY,2014,109(4).
APA Sun, Lulu.,Chen, Chao.,Jiang, Beibei.,Li, Yanli.,Deng, Qiuping.,...&Luo, Jincai.(2014).Grb2-associated binder 1 is essential for cardioprotection against ischemia/reperfusion injury.BASIC RESEARCH IN CARDIOLOGY,109(4).
MLA Sun, Lulu,et al."Grb2-associated binder 1 is essential for cardioprotection against ischemia/reperfusion injury".BASIC RESEARCH IN CARDIOLOGY 109.4(2014).
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