| Title | Grb2-associated binder 1 is essential for cardioprotection against ischemia/reperfusion injury |
| Authors | Sun, Lulu Chen, Chao Jiang, Beibei Li, Yanli Deng, Qiuping Sun, Min An, Xiangbo Yang, Xiao Yang, Ying Zhang, Rongli Lu, Yao Zhu, De-Sheng Huo, Yingqing Feng, Gen-Sheng Zhang, Youyi Luo, Jincai |
| Affiliation | Peking Univ, Lab Vasc Biol, Inst Mol Med, Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China. Peking Univ, Hosp 3, Beijing 100871, Peoples R China. Minist Hlth, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing, Peoples R China. Inst Biotechnol, State Key Lab Prote, Beijing, Peoples R China. Genet Lab Dev & Dis, Beijing, Peoples R China. Peking Univ, Anim Ctr, Beijing 100871, Peoples R China. Univ Calif San Diego, Dept Pathol, Sch Med, San Diego, CA 92093 USA. Peking Univ, Inst Vasc Med, Hosp 3, Beijing 100191, Peoples R China. |
| Keywords | Gab1 Ischemia/reperfusion injury Cardioprotection Cell survival 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 |
| Issue Date | 2014 |
| Publisher | basic research in cardiology |
| Citation | BASIC RESEARCH IN CARDIOLOGY.2014,109,(4). |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/189365 |
| ISSN | 0300-8428 |
| DOI | 10.1007/s00395-014-0420-2 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 分子医学研究所 第三医院 |
