Effects of Erk signal transduction on the cell cycle of rat hepatic stellate cells stimulated by acetaldehyde.
- Author:
Ming-de JIANG
1
;
Hong-de MA
;
Xian-fei ZHONG
;
Fang-wei XIE
;
Wei-zheng ZENG
Author Information
- Publication Type:Journal Article
- MeSH: Acetaldehyde; pharmacology; Animals; Cells, Cultured; Cyclin D1; metabolism; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; metabolism; Enzyme Inhibitors; pharmacology; Flavonoids; pharmacology; Hepatocytes; drug effects; Proto-Oncogene Proteins; Rats
- From: Chinese Journal of Hepatology 2003;11(11):650-653
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of PD98059 on the proliferation and cell cycle of rat hepatic stellate cells (HSCs) stimulated by acetaldehyde and explore its mechanism.
METHODSRat HSCs stimulated by acetaldehyde were incubated with different concentrations of PD98059. Cell proliferation was assessed by MTT colorimetric assay. Cell cycle was analysed by flow cytometry. The mRNA of cyclin D1 and CDK4 were examined by RT-PCR.
RESULTS20, 50, 100 micromol/L PD98059 could significantly inhibit the proliferation of HSCs stimulated by acetaldehyde in a does-dependent manner (0.109+/-0.020, 0.081+/-0.010 and 0.056+/-0.020 vs 0.146+/-0.030, F=31.385, P<0.05) and provoke G0/G1 phase arrest of HSCs stimulated by acetaldehyde in a does-dependent manner (61.9%+/-6.3%, 64.1%+/-3.3% and 70.9%+/-4.8% vs 55.2%+/-4.4%, F=16.402, P<0.05). 50, 100 micromol/L PD98059 could markedly inhibit cyclin D1 mRNA expression of HSC stimulated by acetaldehyde (0.56+/-0.04 and 0.46+/-0.03 vs 0.65+/-0.07, F=68.758, P<0.05) and CDK4 mRNA expression (0.39+/-0.07 and 0.33+/-0.05 vs 0.50+/-0.06, F=29.406, P<0.05).
CONCLUSIONThe Erk signal transduction pathway plays an important role in regulating the proliferation and cell cycle of rat hepatic stellate cells stimulated by acetaldehyde, which may be partly related to its regulative effect on the expression of cyclin D1 gene and CDK4 gene
