β2-Adrenergic receptor-induced transactivation of epidermal growth factor receptor and platelet-derived growth factor receptor via Src kinase promotes rat cardiomyocyte survival

被引：20

作者：

Chen, Hao ^{[1
]}

Ma, Ning ^{[1
]}

Xia, Jing ^{[2
]}

Liu, Jinfen ^{[1
,3
]}

Xu, Zhiwei ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Dept Cardiothorac Surg, Shanghai 200127, Peoples R China

[2] E China Univ Sci & Technol, Sch Biotechnol, Shanghai 200237, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Inst Pediat Translat Med, Shanghai 200127, Peoples R China

来源：

CELL BIOLOGY INTERNATIONAL | 2012年 / 36卷 / 03期

基金：

中国国家自然科学基金;

关键词：

beta(2)-adrenergic receptor; cardiomyocyte; cell viability; epidermal growth factor receptor; platelet-derived growth factor receptor; Src kinase; PROTEIN-COUPLED RECEPTOR; EGF RECEPTOR; TYROSINE KINASE; MEDIATED ACTIVATION; SIGNALING PATHWAY; MYOCYTE APOPTOSIS; CARDIAC MYOCYTES; DNA-SYNTHESIS; C-SRC; CANCER;

D O I：

10.1042/CBI20110162

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Chronic stimulation of the beta-AR (adrenergic receptor) promotes apoptosis of cardiomyocytes, which is implicated in cardiac dysfunction. beta(1)-AR and beta 2-AR are the main subtypes of beta-AR that exert distinct effects on the survival of cardiomyocytes. To clarify the physiological roles of beta(1)-AR and beta(2)-AR in cardiomyocytes, the effects of beta(1)-AR or beta(2)-AR knockdown on the survival of H9c2 cardiomyocytes was investigated. Knockdown of p2-AR, but not beta(1)-AR, suppressed the phosphorylation of EGFR (epidermal growth factor receptor) and PDGFR (platelet-derived growth factor receptor) induced by ISO (isoprenaline). The EGFR inhibitor, AG 1478, attenuated ERK (extracellular-signal-regulated kinase) activation and partially decreased cell survival. Pretreatment with AG 1296, a PDGFR inhibitor, abolished ISO-induced Akt (also known as protein kinase B) phosphorylation and led to a decrease in cell viability. In addition, the Src tyrosine kinase inhibitor, PP2, blocked ISO-mediated both Akt and ERK activation and heavily suppressed viability. Accordingly, in primary neonatal rat cardiomyocytes, the beta(2)-AR inhibitor, but not the beta(1)-AR inhibitor, abrogated the transactivation of EGFR and PDGFR, which was respectively related to Akt and ERK activation. The results show that beta(2)-AR transactivates PDGFR and EGFR, thereby promoting survival of cardiomyocytes.

引用

页码：237 / 244

页数：8

共 29 条

[1]

Neurotensin stimulates mitogenesis of prostate cancer cells through a novel c-Src/Stat5b pathway [J].