Inhibitory effects of tetrandrine on the serum- and platelet-derived growth factor-BB-induced proliferation of rat aortic smooth muscle cells through inhibition of cell cycle progression, DNA synthesis, ERK1/2 activation and c-fos expression

Autor: Tack-Joong Kim, Yong-He Zhang, Guan-Hua Du, Jing-Jie Ma, Bao-Shan Ku, Yeo-Pyo Yun, Hai-Yan Yao, Lian-Hua Fang
Rok vydání: 2003
Předmět:
MAPK/ERK pathway
Male
medicine.medical_specialty
Platelet-derived growth factor
medicine.medical_treatment
Blotting
Western
Myocytes
Smooth Muscle
Becaplermin
Benzylisoquinolines
Polymerase Chain Reaction
Sensitivity and Specificity
Muscle
Smooth
Vascular
Rats
Sprague-Dawley
chemistry.chemical_compound
Alkaloids
Internal medicine
medicine
Animals
Aorta
Cells
Cultured
Probability
Platelet-Derived Growth Factor
Analysis of Variance
Mitogen-Activated Protein Kinase 3
biology
DNA synthesis
Growth factor
Cell Cycle
DNA
Proto-Oncogene Proteins c-sis
Cell cycle
Molecular biology
Rats
Tetrandrine
Enzyme Activation
Endocrinology
chemistry
biology.protein
Mitogen-Activated Protein Kinases
Cardiology and Cardiovascular Medicine
Proto-Oncogene Proteins c-fos
Platelet-derived growth factor receptor
Fetal bovine serum
Cell Division
Zdroj: Atherosclerosis. 174(2)
ISSN: 0021-9150
Popis: Tetrandrine (TET) is a well known naturally occurred nonspecific Ca(2+) channel blocker. It has long been used for the treatment of arrhythmia, hypertension, and occlusive cardiovascular disorders. The objective of the present study was to investigate the effect of TET on the proliferation of primary cultured rat aortic smooth muscle cells (RASMCs). TET significantly inhibited both 10% fetal bovine serum (FBS) and 50 ng/ml platelet-derived growth factor (PDGF)-BB-induced proliferation, [(3) H] ]thymidine incorporation into DNA, and p42/p44 mitogen-activated protein kinase (ERK1/2) phosphorylation at the concentration of 1.0 and 5.0 microM. Flow cytometry analysis of DNA content in synchronized cells revealed blocking of the FBS-inducible cell cycle progression by TET. In accordance with these findings, TET 5 microM caused a 48% decrease in the early elevation of c-fos expression induced after 10% FBS addition. Furthermore, in contrast to its distinguishable higher potency of Ca(2+) antagonistic activity, verapamil showed lower potent antiproliferative activities than TET. These results suggest that TET can exert antiproliferative effects against mitogenic stimuli for RASMCs in vitro by a mechanism that involves the MAPK pathway, altering cell cycle progression, and the inhibitory action cannot be limited to its Ca(2+) modulation.
Databáze: OpenAIRE
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