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学科主题: 公共卫生
题名:
Manganese chloride-induced G0/G1 and S phase arrest in A549 cells
作者: 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
发表日期: 2008-08-19
DOI: 10.1016/j.tox.2008.05.016
卷: 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
所属项目编号: 2002CB512906 ; 30471470
项目资助者: China National Key Basic Research and Development Program ; National Nature Science Foundation of China
WOS记录号: WOS:000258847700006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62592
Appears in Collections:北京大学公共卫生学院_毒理学系_期刊论文

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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

Recommended Citation:
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.
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