摘要
Background Angiotensin Ⅱ （AngⅡ） and platelet-derived growth factor （PDGF）-BB can induce hypertrophy in the cultured rat cardiomyocytes through different signal transduction pathways. Angll stimulates growth through G protein coupled receptor （GPCR）, while PDGF-BB acts via receptor tyrosine kinase （RTK）. Although there has been much development on the individual Angll and PDGF-BB mediated signal pathways, little is known about the interactions between these two factors. Therefore, the crosstalk between Angll and PDGF-BB mediated signal pathways in the rat cardiomyocytes was investigated in this study. Methods Primary culture of neonatal rat ventricular myocytes was prepared. The amount of tyrosine-phosphorylated and non-phosphorylated PDGF-β receptor, Goq/11, and phospholipase C （PLC） β3 were measured by immunoblotting analysis. The statistical analysis was done by one-way ANOVA. Results Tyrosine-phosphorylated PDGF-β receptor was increased by 120.60% at 1 minute and recovered to the control level at 10 minutes after Angll stimulation. Phosphorylation of PDGF-β receptor triggered by Angll was blocked by Iosartan, a specific antagonist of AT1 receptor. PLC inhibitor U73122, protein kinase C （PKC） inhibitor staurosporine （STS） and mitogen-activated ERK activating kinase （MEK） inhibitor PD98059 also inhibited the Angll-induced phosphorylation of PDGF-β receptor. PDGF-BB slightly increased the expression of Gao/11 protein. Conclusion Angll transactivates PDGF-β receptor via AT1 receptor-Gaq/11-PLC-PKC pathway in the rat cardiomyocytes. ERK also participates in the transactivation of PDGF-β receptor triggered by Angll.
Background Angiotensin Ⅱ （AngⅡ） and platelet-derived growth factor （PDGF）-BB can induce hypertrophy in the cultured rat cardiomyocytes through different signal transduction pathways. Angll stimulates growth through G protein coupled receptor （GPCR）, while PDGF-BB acts via receptor tyrosine kinase （RTK）. Although there has been much development on the individual Angll and PDGF-BB mediated signal pathways, little is known about the interactions between these two factors. Therefore, the crosstalk between Angll and PDGF-BB mediated signal pathways in the rat cardiomyocytes was investigated in this study. Methods Primary culture of neonatal rat ventricular myocytes was prepared. The amount of tyrosine-phosphorylated and non-phosphorylated PDGF-β receptor, Goq/11, and phospholipase C （PLC） β3 were measured by immunoblotting analysis. The statistical analysis was done by one-way ANOVA. Results Tyrosine-phosphorylated PDGF-β receptor was increased by 120.60% at 1 minute and recovered to the control level at 10 minutes after Angll stimulation. Phosphorylation of PDGF-β receptor triggered by Angll was blocked by Iosartan, a specific antagonist of AT1 receptor. PLC inhibitor U73122, protein kinase C （PKC） inhibitor staurosporine （STS） and mitogen-activated ERK activating kinase （MEK） inhibitor PD98059 also inhibited the Angll-induced phosphorylation of PDGF-β receptor. PDGF-BB slightly increased the expression of Gao/11 protein. Conclusion Angll transactivates PDGF-β receptor via AT1 receptor-Gaq/11-PLC-PKC pathway in the rat cardiomyocytes. ERK also participates in the transactivation of PDGF-β receptor triggered by Angll.
基金
This study was supported by the grants from the National Natural Science Foundation of China （No. 30470630 and 30570715）, the Program for Changjiang Scholars and Innovative Research Team in University and National Basic Research Program of China （＂973＂ Program, No. 2007CB512004）.
