Crosstalk between angiotensin II and platelet derived growth factor-BB mediated signal pathways in cardiomyocytes
Wang, C.; Wu, L-ling.; Liu, J.; Zhang, Z-guo.; Fan, D.; Li, L.
Chinese Medical Journal 121(3): 236-240
2008
ISSN/ISBN: 0366-6999 PMID: 18298916 Document Number: 618917
Background Angiotensin II (AngII) and platelet-derived growth factor (PDGF)-BB can induce hypertrophy in the cultured rat cardiomyocytes through different signal transduction pathways. Angil 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 Angil and PDGF-BB mediated signal pathways, little is known about the interactions between these two factors. Therefore, the crosstalk between AngII 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-beta receptor, G(aq/11), and phospholipase C (PLC) beta(3) were measured by immunoblotting analysis. The statistical analysis was done by one-way ANOVA.Results Tyrosine-phosphorylated PDGF-beta receptor was increased by 120.60% at 1 minute and recovered to the control level at 10 minutes after AngII stimulation. Phosphorylation of PDGF-P receptor triggered by AngII was blocked by losartan, a specific antagonist of AT(1) receptor. PLC inhibitor U73122, protein kinase C (PKC) inhibitor staurosporine (STS) and mitogen-activated ERK activating kinase (MEK) inhibitor PD98059 also inhibited the AngII-induced phosphorylation of PDGF-beta receptor. PDGF-BB slightly increased the expression of Gq/11 protein.Conclusion AngII transactivates PDGF-beta receptor via AT(1) receptor-G(aq/11)-PLC-PKC pathway in the rat cardiomyocytes. ERK also participates in the transactivation of PDGF-beta receptor triggered by AngII.