The inhibitory effect and mechanism of luteolin 7-glucoside on rat aortic vascular smooth muscle cell proliferation.
The abnormal proliferation of aortic vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty and possibly also in the development of hypertension. The present study was designed to examine the inhibitory effects and the mechanism of luteolin 7-glucoside (L7G) on the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs. L7G significantly inhibited the PDGF-BB-induced proliferation and the DNA synthesis of the VSMCs in a concentration-dependent manner. Pre-incubation of the VSMCs with L7G significantly inhibited the PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the phospholipase C (PLC)-gamma1 activation. However, L7G had almost no affect on the phosphorylation of PDGF-beta receptor tyrosine kinase, which was induced by PDGF-BB. These results suggest that L7G inhibits the PDGF-BB-induced proliferation of VSMCs via the blocking of PLC-gamma1, Akt, and ERK1/2 phosphorylation.
Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Tack-Joong
TJ
Kim
Jin-Ho
JH
Kim
Yong-Ri
YR
Jin
Yeo-Pyo
YP
Yun
D000199:Actins / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005960:Glucosides / Q000494:pharmacology*; D047311:Luteolin / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008958:Models, Molecular; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
D000199:Actins; D005960:Glucosides; D010982:Platelet-Derived Growth Factor; C066408:luteolin-7-glucoside; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D051966:Phospholipase C gamma; D047311:Luteolin; D013936:Thymidine