丙型肝炎病毒核心蛋白对核转录因子stat3活性的调控作用  

Regulation of hepatitis C virus core protein on the activity of signal transducers and activators of transcription 3

作　　者：冯德云[1] 李波[1] 郑晖[1] 程瑞雪[1] 曹亚[2] 

机构地区：[1]中南大学基础医学院病理学系,长沙410078 [2]中南大学肿瘤研究所,长沙410078

出　　处：《中南大学学报（医学版）》2005年第6期631-635,共5页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(30270601)

摘　　要：目的:探讨丙型肝炎病毒(HCV)核心蛋白对核转录因子stat3活性的调控作用。方法:将表达HCV核心蛋白的真核细胞表达质粒pcDNA3.1-core转染人源肝细胞系QSG7701,建立稳定表达HCV核心蛋白的细胞株QSG7701-core,利用免疫细胞化学、W estern b lot及凝胶电泳迁移实验(EMSA)等方法检测stat3的磷酸化及DNA结合活性。结果:在表达HCV核心蛋白的QSG7701细胞中,stat3的磷酸化水平明显低于空白质粒转染组和未转染组,而总stat3的表达水平3组无明显差别;核内磷酸化的stat3阳性信号明显减弱;stat3的DNA的结合活性明显低于空白质粒转染组和未转染组。结论:在人源永生化肝细胞系中HCV核心蛋白的表达可能具有抑制stat3的磷酸化和DNA结合活性的作用,从而抑制JAK/stat3信号转导通路活化,这可能是HCV干扰素治疗效果不佳的原因之一。Objective To investigate the regulation of hepatitis C virus （HCV） core protein on the activity of signal transducers and activators of transcription 3 （ stat3 ）. Methods A cell line expressing stable HCV core protein-QSG7701-core was constructed by transfecting the pcDNA3. 1-core （expressing HCV core protein） into the human immortalized hepatocyte line QSG7701. The phosphorylation and DNA binding activity of stat3 were detected by immunocytochemistry, Western blot, and electrophoretic mobility shift assay （ EMSA ）. Results The expression level of phosphorylated stat3 in QSG7701-core cells was significantly lower than that in QSG7701-pcDNA3. 1 cells and untransfected QSG7701 cells, but there were no significant differences in the expression levels of total stat3 among the 3 groups. The positive signal of phosphorylated stat3 in nucleus of QSG7701-core cells was obviously weaker than that in QSG7701-pcDNA3. 1 cells and untransfected QSG7701 cells. EMSA showed that DNA binding activity of stat3 in QSG7701-core cells significantly decreased. Conclusion The expression of HCV core protein in human hepatocyte line may suppress the phosphorylation and DNA binding activity of stat3, which may be one of the causes for resistance against interferon.

关 键 词：丙型肝炎病毒 核心蛋白 肝细胞 核转录因子 

分 类 号：R373.21[医药卫生—病原生物学]