Gab1 Is Modulated by Chronic Hypoxia in Children with Cyanotic Congenital Heart Defect and Its Overexpression Reduces Apoptosis in Rat Neonatal Cardiomyocytes.
Gab1 Is Modulated by Chronic Hypoxia in Children with Cyanotic Congenital Heart Defect and Its Overexpression Reduces Apoptosis in Rat Neonatal Cardiomyocytes.
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DOI：
10.1155/2015/718492
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发表时间：
2015
影响因子：
--
通讯作者：
Ghorbel MT
中科院分区：
文献类型：
--
作者：
Cherif M;Caputo M;Nakaoka Y;Angelini GD;Ghorbel MT
Gab1（Grb2 相关结合蛋白 1）是支架/对接蛋白（Gab1、Gab2 和 Gab3）的成员。它是成纤维细胞存活和维持心脏功能所必需的。关于慢性缺氧时人类 Gab1 的表达知之甚少。本研究检验了缺氧调节人儿科心肌和培养的大鼠心肌细胞中 Gab1 表达的假设。在这里，我们发现Gab1在紫绀型和紫绀型先天性心脏缺陷儿童的心肌组织中表达。与无紫绀心脏相比，Gab1 蛋白在紫绀心脏中上调，表明 Gab1 上调是紫绀儿童缺氧启动的生存程序的一个组成部分。其他 Gab1 相互作用伙伴的表达不受缺氧和 Gab1 调节的影响。此外，使用体外模型，我们证明在缺氧条件下，新生儿心肌细胞中过度表达 Gab1 会导致细胞凋亡减少，表明该蛋白在心肌细胞存活中发挥作用。总而言之，我们的数据提供了强有力的证据，证明 Gab1 对于缺氧应激后心脏细胞的存活很重要。
Gab1 (Grb2 associated binding protein 1) is a member of the scaffolding/docking proteins (Gab1, Gab2, and Gab3). It is required for fibroblast cell survival and maintaining cardiac function. Very little is known about human Gab1 expression in response to chronic hypoxia. The present study examined the hypothesis that hypoxia regulates Gab1 expression in human paediatric myocardium and cultured rat cardiomyocytes. Here we showed that Gab1 is expressed in myocardial tissue in acyanotic and cyanotic children with congenital heart defects. Gab1 protein was upregulated in cyanotic compared to acyanotic hearts suggesting that Gab1 upregulation is a component of the survival program initiated by hypoxia in cyanotic children. The expression of other Gab1 interacting partners was not affected by hypoxia and Gab1 regulation. Additionally, using an in vitro model, we demonstrated that overexpressing Gab1 in neonatal cardiomyocytes, under hypoxic condition, resulted in the reduction of apoptosis suggesting a role for this protein in cardiomyocyte survival. Altogether, our data provide strong evidence that Gab1 is important for heart cell survival following hypoxic stress.
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影响因子：
37.8
作者：
Matoba, S;Tatsumi, T;Nakagawa, M
通讯作者：
Nakagawa, M
DOI：
10.1073/pnas.0909570107
发表时间：
2010-03-30
影响因子：
11.1
作者：
Ren, Hongxia;Accili, Domenico;Duan, Cunming
通讯作者：
Duan, Cunming
影响因子：
3.8
作者：
Littlejohns B;Heesom K;Angelini GD;Suleiman MS
通讯作者：
Suleiman MS
影响因子：
5.3
作者：
Holgado-Madruga, M;Wong, AJ
通讯作者：
Wong, AJ
DOI：
10.1152/ajpheart.00053.2003
发表时间：
2003-09-01
影响因子：
4.8
作者：
Sala-Newby, GB;Freeman, NVE;Newby, AC
通讯作者：
Newby, AC