Overexpression of Shp-2 attenuates apoptosis in neonatal rat cardiac myocytes through the ERK pathway

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• 作者：Guoyuan Wang^a ; ^b ; ¹ ; Chengyan Jin^a ; ¹ ; Yuanyuan Hou^a ; ¹ ; Lijing Zhang^a ; Shanshan Li^a ; Luquan Zhang^a ; Bo Wu^a ; Quanfeng Li^a ; Changqing Xu^a ; Ye Tian^a ; Li Zhang^a ; ^{zhangli@ems.hrbmu.edu.cn}
• 关键词：Shp-2 ; Src homology 2 domain-containing protein tyrosine phosphatase 2 ; Cyt C ; cytochrome C ; PTP ; protein tyrosine phosphatase ; ERK ; extracellular signal-regulated protein kinase ; MAPK ; mitogen-activated protein kinase ; EGCG ; epigallocatechin-3-gallate
• 刊名：Experimental and Molecular Pathology
• 出版年：2012
• 期刊代码：291_00144800
• 类别：med
• 出版时间：August, 2012
• 卷：93
• 期：1
• 页码：50-55
• 文件大小：708 K

摘要

During cardiac ischemia and end-stage heart disease, a large number of cardiac cells are apoptotic, and therefore, heart function is impaired. Although the role of Shp-2 in cell survival has been reported, its regulation of cardiac apoptosis is still undetermined.

To better understand the potential role of Shp-2 in apoptosis, cell death was determined in serum-depleted cardiomyocytes. Shp-2 was inhibited by NSC87877, and apoptosis, Cyt C release and caspase 3 activation were determined. To evaluate the notion that Shp-2 plays a role in survival stimulation, wild-type and gain-of-function mutant Shp-2 adenoviruses were infected into neonatal cardiomyocytes, and ERK activation was examined. Finally, the MEK inhibitor U0126 was utilized to block the ERK pathway and determine the role of Shp-2 in this pathway.

We found that Shp-2 inhibition enhanced apoptosis via regulation of mitochondrial Cyt C release and activation of caspase 3. Overexpression of Shp-2 inhibited apoptosis through activation of ERK. The MEK inhibitor U0126 abolished Shp-2's effect on apoptosis in cardiomyocytes.

Our results have revealed that Shp-2 functions as an intracellular inhibitor of apoptosis. These data provide insight into the pathogenesis and the therapeutic strategies of heart diseases.