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01.07.2014 | Original Contribution

Grb2-associated binder 1 is essential for cardioprotection against ischemia/reperfusion injury

verfasst von: Lulu Sun, Chao Chen, Beibei Jiang, Yanli Li, Qiuping Deng, Min Sun, Xiangbo An, Xiao Yang, Ying Yang, Rongli Zhang, Yao Lu, De-Sheng Zhu, Yingqing Huo, Gen-Sheng Feng, Youyi Zhang, Jincai Luo

Erschienen in: Basic Research in Cardiology | Ausgabe 4/2014

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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.

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Titel: Grb2-associated binder 1 is essential for cardioprotection against ischemia/reperfusion injury
verfasst von: Lulu Sun
Chao Chen
Beibei Jiang
Yanli Li
Qiuping Deng
Min Sun
Xiangbo An
Xiao Yang
Ying Yang
Rongli Zhang
Yao Lu
De-Sheng Zhu
Yingqing Huo
Gen-Sheng Feng
Youyi Zhang
Jincai Luo
Publikationsdatum: 01.07.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 4/2014
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-014-0420-2

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Grb2-associated binder 1 is essential for cardioprotection against ischemia/reperfusion injury

Abstract

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„Jeder Fall von plötzlichem Tod muss obduziert werden!“

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

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Abstract

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