title: β2-Adrenergic receptor-induced transactivation of epidermal growth factor receptor and platelet-derived growth factor receptor via Src kinase promotes rat cardiomyocyte survival.
abstract: Chronic stimulation of the β-AR (adrenergic receptor) promotes apoptosis of cardiomyocytes, which is implicated in cardiac dysfunction. β1-AR and β2-AR are the main subtypes of β-AR that exert distinct effects on the survival of cardiomyocytes. To clarify the physiological roles of β1-AR and β2-AR in cardiomyocytes, the effects of β1-AR or β2-AR knockdown on the survival of H9c2 cardiomyocytes was investigated. Knockdown of β2-AR, but not β1-AR, suppressed the phosphorylation of EGFR (epidermal growth factor receptor) and PDGFR (platelet-derived growth factor receptor) induced by ISO (isoprenaline). The EGFR inhibitor, AG1478, attenuated ERK (extracellular-signal-regulated kinase) activation and partially decreased cell survival. Pretreatment with AG1296, 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 β2-AR inhibitor, but not the β1-AR inhibitor, abrogated the transactivation of EGFR and PDGFR, which was respectively related to Akt and ERK activation. The results show that β2-AR transactivates PDGFR and EGFR, thereby promoting survival of cardiomyocytes.
authors.affiliation: Department of Cardiothoracic Surgery, Shanghai Childrens Medical Center, Shanghai JiaoTong University School of Medicine, Shanghai, Peoples Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
authors.forename: Jinfen
authors.initials: J
authors.lastname: Liu
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D002470:Cell Survival; D066246:ErbB Receptors / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015533:Transcriptional Activation; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D019061:src-Family Kinases