Cross-talk between ERK and NF-kappaB signal transduction pathways in the hepatocytes expressing hepatitis C virus nonstructural protein 3.
- Author:
Hui GUO
1
;
De-Yun FENG
;
Bo LI
;
Qiong-Qiong HE
;
Shu-Yan SUN
;
Rui-Xue CHENG
Author Information
1. Department of Pathology, College of Basic Medicine, Central South University, Changsha, China.
- Publication Type:Journal Article
- MeSH:
Blotting, Western;
Cell Cycle;
drug effects;
Cell Line;
Cell Proliferation;
drug effects;
Cyclin D1;
metabolism;
Dose-Response Relationship, Drug;
Extracellular Signal-Regulated MAP Kinases;
antagonists & inhibitors;
metabolism;
Flavonoids;
pharmacology;
Hepatocytes;
cytology;
metabolism;
Humans;
NF-kappa B;
metabolism;
Phosphorylation;
drug effects;
Signal Transduction;
drug effects;
physiology;
Viral Nonstructural Proteins;
genetics;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2007;32(2):259-263
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the cross-talk between extracellular signal-regulated kinase (ERK) and nuclear factor (NF-kappaB) signal transduction pathways in the hepatocytes expressing hepatitis C virus nonstructural protein 3 (HCV NS3).
METHODS:A cell line QSG7701/NS3, which stably expressed HCV NS3 protein, was constructed by transfecting plasmid pcDNA3.1-NS3 into a human immortalized hepatocyte line QSG7701. Before and after QSG7701/NS3 cells were treated by MEK inhibitor PD98059, the phosphorylation level of ERK and the expression of cyclin D1 protein were detected by Western blot; the DNA binding activities of activator protein 1 (AP-1) and NF-kappaB were evaluated with electrophoretic mobility shift assay (EMSA). Cell cycles were measured by flow cytometry (FCM); the effects of PD98059 on the cell proliferation were determined by MTT assay.
RESULTS:HCV NS3 protein could up-regulate the phosphorylation of ERK and the expression level of cyclin D1 in QSG7701 cells. PD98059 could inhibit the cell proliferation mediated by HCV NS3 protein, down-regulate the activities of AP-1 and NF-kappaB, and suppress the expression of cyclin D1.
CONCLUSION:The inhibition of ERK can suppress the DNA binding activity of NF-kappaB and the cell proliferation mediated by HCV NS3 protein in a dose-dependent manner. There may be a cross-talk between ERK and NF-kappaB signal transduction pathways, which may exert synergistic action on the proliferation and malignant transformation of hepatocytes.
