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学科主题: 临床医学
题名:
Grb2-associated binder 1 is essential for cardioprotection against ischemia/reperfusion injury
作者: 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
发表日期: 2014-06-21
DOI: 10.1007/s00395-014-0420-2
卷: 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
所属项目编号: 91339111 ; 81170098 ; 31221002 ; 2007CB512100 ; 5082009 ; 2011CB503903 ; 81030001 ; 30910103902 ; 2009ZX09501-027 ; NIHR01HL096125
项目资助者: 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
WOS记录号: WOS:000338319800001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59825
Appears in Collections:北京大学第三临床医学院_期刊论文

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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

Recommended Citation:
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).
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