Inhibition of PDGF beta-receptor tyrosine phosphorylation and its downstream intracellular signal transduction in rat aortic vascular smooth muscle cells by kaempferol.
Kaempferol, a flavonoid present in human diet and plants, has been known to show cardiovascular protection via its anti-oxidant activity. In this study, we have investigated the effect of kaempferol on the proliferation of primary cultured rat aortic vascular smooth muscle cells (VSMCs). Kaempferol significantly inhibited 50 ng/mL platelet-derived growth factor (PDGF)-BB-induced proliferation and [3H]-thymidine incorporation into DNA at concentrations of 5, 20 and 50 microM without any cytotoxicity. Kaempferol also inhibited the c-fos mRNA expression induced by PDGF-BB concentration-dependently. In addition, consistent with the inhibition of cell proliferation and c-fos mRNA expression, kaempferol inhibited the PDGF beta-receptor (Rbeta) phosphorylation in a concentration-dependent manner. Accordingly, the downstream signal transductions of PDGF-Rbeta such as ERK1/2, Akt and PLC-gamma1 phosphorylation were also inhibited by kaempferol in the same pattern. These findings suggest that, in addition to its anti-oxidant activity, the cardiovascular protective effect of kaempferol may be mediated, at least in part, by the suppression of VSMC proliferation, which is due to the inhibition of PDGF-Rbeta tyrosine phosphorylation and its downstream intracellular signal transduction.
Kim
Soo-Yeon
SY
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Korea.
Jin
Yong-Ri
YR
Lim
Yong
Y
Kim
Jin-Ho
JH
Cho
Mi-Ra
MR
Hong
Jin-Tae
JT
Yoo
Hwan-Soo
HS
Yun
Yeo-Pyo
YP
D000818:Animals; D001011:Aorta / Q000166:cytology; D000077214:Becaplermin; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D044949:Kaempferols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010946:Plants, Medicinal; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000187:drug effects*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D044949:Kaempferols; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D014443:Tyrosine; C006552:kaempferol; D020797:Receptor, Platelet-Derived Growth Factor beta