A decrease in cyclin B1 levels leads to polyploidization in DNA damage-induced senescence
A decrease in cyclin B1 levels leads to polyploidization in DNA damage-induced senescence
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DOI：
10.1042/cbi20090398
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发表时间：
2010-06-01
影响因子：
3.9
通讯作者：
Yamaguchi, Naoto
中科院分区：
文献类型：
--
作者：
Kikuchi, Ikue;Nakayama, Yuji;Yamaguchi, Naoto
阿霉素是一种蒽环类抗生素，已用于治疗各种类型的肿瘤。阿霉素以浓度依赖性方式诱导至少两种不同类型的生长抑制，如衰老和凋亡。细胞衰老是细胞不能进一步增殖的状态，并且衰老细胞经常显示多倍性。虽然细胞分裂的终止被认为与多倍化相关，但衰老细胞中多倍化诱导的潜在机制在很大程度上尚不清楚。因此，我们希望探讨细胞周期蛋白B1水平在阿霉素诱导的衰老细胞多倍化中的作用。亚细胞毒性浓度的阿霉素诱导的多倍体细胞具有衰老的特征，如扁平和扩大的细胞形状和激活的β-半乳糖苷酶活性。在DNA损伤诱导的衰老细胞中，细胞周期蛋白B1的水平短暂增加，随后下降。细胞周期蛋白B 1水平的下降发生在G2细胞多倍体化过程中，亚细胞毒性浓度的阿霉素治疗后。与此相反，既不多倍体，也不减少细胞周期蛋白B1水平诱导治疗与细胞毒性浓度的阿霉素。这些结果表明，细胞周期蛋白B1水平的降低是由DNA损伤引起的，导致DNA损伤诱导的衰老中的多倍化。
Adriamycin, an anthracycline antibiotic, has been used for the treatment of various types of tumours. Adriamycin induces at least two distinct types of growth repression, such as senescence and apoptosis, in a concentration-dependent manner. Cellular senescence is a condition in which cells are unable to proliferate further, and senescent cells frequently show polyploidy. Although abrogation of cell division is thought to correlate with polyploidization, the mechanisms underlying induction of polyploidization in senescent cells are largely unclear. We wished, therefore, to explore the role of cyclin B1 level in polyploidization of Adriamycin-induced senescent cells. A subcytotoxic concentration of Adriamycin induced polyploid cells having the features of senescence, such as flattened and enlarged cell shape and activated beta-galactosidase activity. In DNA damage-induced senescent cells, the levels of cyclin B1 were transiently increased and subsequently decreased. The decrease in cyclin B 1 levels occurred in G2 cells during polyploidization upon treatment with a subcytotoxic concentration of Adriamycin. In contrast, neither polyploidy nor a decrease in cyclin B1 levels was induced by treatment with a cytotoxic concentration of Adriamycin. These results suggest that a decrease in cyclin B1 levels is induced by DNA damage, resulting in polyploidization in DNA damage-induced senescence.