Preferential Fas-mediated apoptotic execution at G1 phase: the resistance of mitotic cells to the cell death.
Preferential Fas-mediated apoptotic execution at G1 phase: the resistance of mitotic cells to the cell death.
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DOI：
10.1038/cddis.2012.52
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发表时间：
2012-05-24
影响因子：
9
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细胞凋亡由细胞外和细胞内环境产生的各种应激诱导。细胞周期的保真度由监视机制监测，如果任何关键过程尚未完成或损伤持续，则会阻止其进一步进展，然后有问题的细胞进行凋亡。尽管细胞周期和细胞凋亡调控的分子机制已被阐明，但它们之间的联系尚不清楚，尤其是细胞周期与死亡受体介导的细胞凋亡之间的联系。通过使用HeLa.S-Fucci（基于荧光泛素化的细胞周期指示剂）细胞，我们研究了细胞周期进程与凋亡执行之间的关系。为了监测细胞周期进程中的凋亡执行，我们用延时荧光显微镜观察诱导凋亡后的细胞。在随机培养的细胞中，约70%的Fas介导的凋亡细胞处于G1期，约20%的细胞在胞质分裂后立即死亡，而超过60%的依托泊苷诱导的凋亡细胞处于S/G2期。这些结果通过使用细胞的同步培养来证实。此外，有丝分裂细胞表现出抵抗Fas介导的凋亡。总之，这些研究结果表明，凋亡的执行是依赖于细胞周期时相和Fas介导的凋亡优先发生在G1期。
Apoptosis is induced by various stresses generated from the extracellular and intracellular environments. The fidelity of the cell cycle is monitored by surveillance mechanisms that arrest its further progression if any crucial process has not been completed or damages are sustained, and then the cells with problems undergo apoptosis. Although the molecular mechanisms involved in the regulation of the cell cycle and that of apoptosis have been elucidated, the links between them are not clear, especially that between cell cycle and death receptor-mediated apoptosis. By using the HeLa.S-Fucci (fluorescent ubiquitination-based cell cycle indicator) cells, we investigated the relationship between the cell cycle progression and apoptotic execution. To monitor apoptotic execution during cell cycle progression, we observed the cells after induction of apoptosis with time-lapse fluorescent microscopy. About 70% of Fas-mediated apoptotic cells were present at G1 phase and about 20% of cells died immediately after cytokinesis, whereas more than 60% of etoposide-induced apoptotic cells were at S/G2 phases in random culture of the cells. These results were confirmed by using synchronized culture of the cells. Furthermore, mitotic cells showed the resistance to Fas-mediated apoptosis. In conclusion, these findings suggest that apoptotic execution is dependent on cell cycle phase and Fas-mediated apoptosis preferentially occurs at G1 phase.