中文摘要：

目的：探讨在CH1细胞中过氧化物酶体增殖物受体γ共激活因子1α（PGC-1α）调控细胞周期时三磷酸腺苷（ATP）和活性氧（ROS）的作用机制。创新点：构建了稳定表达PGC-1α的CH1细胞株,并系统地研究了PGC-1α调控细胞周期是通过ATP和ROS调节CyclinD1和CyclinB1的行使功能。方法：以慢病毒质粒pBABE为载体构建了PGC-1α稳定表达的CH1 PGC-1α细胞株（PGC-1α）,同时转染空质粒pBABE作为对照（PB）,结合RNA干扰CH1 PGC-1α中PGC-1α的过表达（Si）,测定了ATP和ROS水平。用流式细胞术检测了细胞周期和免疫印迹检测了CyclinB1/D1的表达,并进一步分别用寡霉素抑制PGC-1α细胞中的ATP生成,用H2O2处理细胞以增加外源ROS水平。然后检测ATP和ROS改变后,对CyclinB1/D1表达及细胞周期的影响,以明确ATP和ROS是否参与PGC-1α对细胞周期的调控作用。结论：本实验成功构建了稳定表达PGC-1α的细胞株（图1和图2a）,与PB对照和RNA干扰PGC-1α比较,过表达PGC-1α具有升高ATP、降低ROS和促进细胞周期的作用（图3和图4）。进一步用寡霉素抑制ATP合成后发现CyclinD1明显下调（图5）,而加入H2O2增加外源ROS后发现CyclinB1显著上调（图6）。通过本实验我们提出PGC-1α调控细胞周期是通过升高ATP水平抑制CyclinD1表达和降低ROS水平促进CyclinB1表达来实现。

英文摘要：

Peroxisome proliferator-activated receptor-γ coactivator 1α（PGC-1α） is a transcriptional co-activator involved in mitochondrial biogenesis, respiratory capacity, and oxidative phosphorylation（OXPHOS）. PGC-1α plays an important role in cellular metabolism and is associated with tumorigenesis, suggesting an involvement in cell cycle progression. However, the underlying mechanisms mediating its involvement in these processes remain unclear. To elucidate the signaling pathways involved in PGC-1α function, we established a cell line, CH1 PGC-1α, which stably overexpresses PGC-1α. Using this cell line, we found that over-expression of PGC-1α stimulated extra adenosine triphosphate（ATP） and reduced reactive oxygen species（ROS） production. These effects were accompanied by up-regulation of the cell cycle checkpoint regulators Cyclin D1 and Cyclin B1. We hypothesized that ATP and ROS function as cellular signals to regulate cyclins and control cell cycle progression. Indeed, we found that reduction of ATP levels down-regulated Cyclin D1 but not Cyclin B1, whereas elevation of ROS levels down-regulated Cyclin B1 but not Cyclin D1. Furthermore, both low ATP levels and elevated ROS levels inhibited cell growth, but PGC-1α was maintained at a constant level. Together, these results demonstrate that PGC-1α regulates cell cycle progression through modulation of Cyclin D1 and Cyclin B1 by ATP and ROS. These findings suggest that PGC-1α potentially coordinates energy metabolism together with the cell cycle.