Crosstalk between angiotensin II and platelet derived growth factor-BB mediated signal pathways in cardiomyocytes.
BACKGROUND
Angiotensin II (AngII) and platelet-derived growth factor (PDGF)-BB can induce hypertrophy in the cultured rat cardiomyocytes through different signal transduction pathways. AngII 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 AngII 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(alphaq/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-beta receptor triggered by AngII was blocked by losartan, 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 AngII-induced phosphorylation of PDGF-beta receptor. PDGF-BB slightly increased the expression of G(alphaq/11) protein.


CONCLUSIONS
AngII transactivates PDGF-beta receptor via AT(1) receptor-G(alphaq/11)-PLC-PKC pathway in the rat cardiomyocytes. ERK also participates in the transactivation of PDGF-beta receptor triggered by AngII.
Wang
Cheng
C
Department of Physiology and Pathophysiology and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100083, China.
Wu
Li-ling
LL
Liu
Jie
J
Zhang
Zhi-guo
ZG
Fan
Dong
D
Li
Li
L
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D002478:Cells, Cultured; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000804:Angiotensin II; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D010738:Type C Phospholipases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11