文献类型：期刊文献

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

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

年份：2012

卷号：36

期号：3

起止页码：237

外文期刊名：CELL BIOLOGY INTERNATIONAL

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000301466600002)】；

基金：This work was supported by the National Natural Science Foundation of China [grant number 30772143].

语种：英文

外文关键词：beta(2)-adrenergic receptor; cardiomyocyte; cell viability; epidermal growth factor receptor; platelet-derived growth factor receptor; Src kinase

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.