Hepatitis C virus core protein induces apoptosis and impairs cell-cycle regulation in stably transformed Chinese hamster ovary cells
Hepatitis C virus core protein induces apoptosis and impairs cell-cycle regulation in stably transformed Chinese hamster ovary cells
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DOI：
10.1053/jhep.2000.7985
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发表时间：
2000-06-01
期刊：
影响因子：
13.5
通讯作者：
Lemon, SM
中科院分区：
文献类型：
--
作者：
Honda, M;Kaneko, S;Lemon, SM
丙型肝炎病毒（HCV）感染与肝细胞癌的发生有关。多项证据表明，HCV 的核心蛋白可能在这种癌症的发展中发挥作用。作者研究了源自中国仓鼠卵巢 (CHO-K1) 细胞的稳定细胞系中细胞周期的调节，这些细胞组成型表达一种或多种 HCV 结构蛋白。在含有低浓度血清（血清饥饿）的培养基中，表达核心蛋白的细胞系显示出比非核心表达细胞明显更少的活细胞群。核心表达细胞的低活力是由于经历凋亡的细胞数量增加造成的。有趣的是，细胞周期分析表明，G(0)处的阻滞功能受损，即使在血清饥饿下，核心表达细胞系的细胞周期也会加速。因此，HCV核心蛋白使细胞凋亡对血清饥饿敏感，尽管它促进CHO-K1细胞中的细胞周期。为了解释这些发现，作者检查了复兴细胞凋亡和细胞周期相关基因的表达。响应血清饥饿，核心表达细胞中 c-myc 基因的表达被显着诱导。 c-myc、p53、p21WAF1/CIP1 和 Bax 下游的其他凋亡诱导基因被显着高度诱导，但没有诱导 Bcl-2，而 Bcl-2 可防止核心表达细胞的凋亡。因此，HCV核心蛋白通过激活c-myc表达诱导细胞凋亡并损害细胞周期的调节，而p53和Bax途径在诱导细胞凋亡中发挥作用。
Hepatitis C virus (HCV) infection is associated with the development of hepatocellular carcinoma. Several lines of evidence suggest that the core protein of HCV may play a role in the development of this cancer. The authors examined regulation of the cell cycle in stable cell lines derived from Chinese hamster ovary (CHO-K1) cells that constitutively expressed one or more of the structural proteins of HCV. In media containing low concentrations of serum (serum starvation), cell lines expressing the core protein showed a significantly lower population of viable cells than noncore-expressing cells. The low viability of the core-expressing cells was a result of the increased population of cells undergoing apoptosis. Interestingly, the cell cycle analysis revealed that the arresting function at G(0) was impaired, and the cell cycle was accelerated in core-expressing cell lines even under serum starvation. Thus, the HCV core protein sensitizes the apoptosis to serum starvation, although it promotes the cell cycle in CHO-K1 cells. To explain these findings, the authors examined the expression of revival apoptosis and cell-cycle-related genes. Expression of the c-myc genes was significantly induced in core-expressing cells in response to serum starvation. Other apoptosis-inducing genes downstream of c-myc, p53, p21WAF1/CIP1 and Bax were significantly highly induced, although there was no induction of Bcl-2, which prevents apoptosis in core-expressing cells. Thus, the HCV core protein induced apoptosis and impaired the regulation of the cell cycle by activating c-myc expression, whereas the p53 and Bax pathways play a role in the induction of apoptosis.