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Manganese chloride-induced G0/G1 and S phase arrest in A549 cells
Zhao, Peng1; Zhong, Weijian2; Ying, Xianping2; Yuan, Zhun1; Fu, Juanling1; Zhou, Zongcan1
关键词manganese chloride cell cycle Cdk2 Cdk4 p53 A549 cells
刊名TOXICOLOGY
2008-08-19
DOI10.1016/j.tox.2008.05.016
250期:1页:39-46
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]Pharmacology & Pharmacy ; Toxicology
关键词[WOS]CYCLE ; REPLICATION ; CHECKPOINTS ; PROGRESSION ; INHIBITORS ; EXPRESSION ; PROTEIN ; KINASES ; BRAIN ; CDK2
英文摘要

In the present study, we investigated the effects of manganese chloride (MnCl(2)) on cell cycle progression in A549 cells used as a model of Mn-induced lung toxicity. Cells were treated with various concentrations of MnCl(2) (0, 0.01. 0.1, 0.5, 1.0 or 2.0 mM) for 24,48 or 72 h. Cell proliferation was determined with MTT assay and mitotic index measurement and apoptosis was measured by flow cytometer. The results showed that MnCl(2) inhibited A549 cells proliferation in a dose- and time-dependent manner, and induced apoptosis in A549 cells. When G0/G1 cells obtained by serum starvation were incubated with 0.5 mM of MnCl(2) in the presence of 10% serum for several time intervals, the disruption of cell cycle progression was observed. The G0/G1 arrest was induced by MnCl(2) treatment at 16 h and the arrest maintained for 8 h. Following the G0/G1 arrest, MnCl(2) blocked the cells at S phase at 28 h and the S phase arrest maintained for at least 4 h. And moreover, proteasome inhibitor MG132 was able to prolong the duration of G0/G1 arrest induced by MnCl(2) treatment. Results of western blotting assay revealed that cellular Cdk4, Cdk2 and phospho-Cdk2 (Thr160) levels decreased in manganese-treated cells at both 20 and 28 h. In addition, the decreasing of Cyclin A level and the increasing of p53 and WAF1/p21 were also induced by MnCl(2) treatment at 20 h. The expression of Cyclin D1, Cyclin E and Cdc25A proteins was not altered in manganese-treated cells at both 20 and 28 h. Our results indicate that MnCl(2) orderly induces G0/G1 and S phase arrest in A549 cells, the decreasing of Cdk4, Cdk2 and Cyclin A, and the increasing of p53 and Cdks inhibitor WAF1/p21 might be responsible for the G0/G1 arrest, and the decreasing of Cdk4 and Cdk2 levels for the S phase arrest. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

语种英语
WOS记录号WOS:000258847700006
项目编号2002CB512906 ; 30471470
资助机构China National Key Basic Research and Development Program ; National Nature Science Foundation of China
引用统计
被引频次:29[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62592
专题北京大学公共卫生学院_毒理学系
北京大学公共卫生学院_公共卫生学院
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Toxicol, Beijing 100083, Peoples R China
2.Shanghai Municipal Ctr Dis Control & Prevent, Dept Toxicol, Shanghai 200336, Peoples R China
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GB/T 7714
Zhao, Peng,Zhong, Weijian,Ying, Xianping,et al. Manganese chloride-induced G0/G1 and S phase arrest in A549 cells[J]. TOXICOLOGY,2008,250(1):39-46.
APA Zhao, Peng,Zhong, Weijian,Ying, Xianping,Yuan, Zhun,Fu, Juanling,&Zhou, Zongcan.(2008).Manganese chloride-induced G0/G1 and S phase arrest in A549 cells.TOXICOLOGY,250(1),39-46.
MLA Zhao, Peng,et al."Manganese chloride-induced G0/G1 and S phase arrest in A549 cells".TOXICOLOGY 250.1(2008):39-46.
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