國家衛生研究院 NHRI:Item 3990099045/2478
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    题名: ATM/ATR-related checkpoint signals mediate arsenite-induced G(2)/M arrest in primary aortic endothelial cells
    作者: Tsou, TC;Tsai, FY;Yeh, SC;Chang, LW
    贡献者: Division of Environmental Health and Occupational Medicine
    摘要: Epidemiological studies have demonstrated a high association of inorganic arsenic exposure with vascular disease. Our recent in vitro studies have linked this vascular damage to vascular endothelial dysfunction induced by arsenic exposure. However, cell-cycle arrest induced by arsenic and its involvement in vascular dysfunction remain to be clarified. In this study, we employed primary porcine aortic endothelial cells to investigate regulatory mechanisms of G(2)/M phase arrest induced by arsenite. Our study revealed that lower concentrations of arsenite (1 and 3 mu M) increased cell proliferation, whereas higher concentrations of arsenite (10, 20, and 30 mu M) inhibited cell proliferation together with correlated increases in G(2)/M phase arrest. We found that this arsenite-induced G(2)/M phase arrest was accompanied by accumulation and/or phosphorylation of checkpoint-related molecules, including p53, Cdc25B, Cdc25C, and securin. Inhibition of activations of these checkpoint-related molecules by caffeine significantly attenuated the 30-mu M arsenite-induced G(2)/M phase arrest by 93%. Our data suggest that the DNA damage responsive kinases ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) play critical roles in arsenite-induced G(2)/M phase arrest in aortic endothelial cells possibly via regulation of checkpoint-related signaling molecules including p53, Cdc25B, Cdc25C, and securin.
    关键词: Toxicology
    日期: 2006-12
    關聯: Archives of Toxicology. 2006 Dec;80(12):804-810.
    Link to: http://dx.doi.org/10.1007/s00204-006-0110-4
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0340-5761&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000242334300002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33751518046
    显示于类别:[張惠華(1999-2009)] 期刊論文
    [鄒粹軍] 期刊論文

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