國家衛生研究院 NHRI:Item 3990099045/2478

NHRI > National Institute of Environmental Health Sciences > Louis W. Chang(1999-2009) > Periodical Articles > Item 3990099045/2478

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2478

Title:	ATM/ATR-related checkpoint signals mediate arsenite-induced G(2)/M arrest in primary aortic endothelial cells
Authors:	Tsou, TC;Tsai, FY;Yeh, SC;Chang, LW
Contributors:	Division of Environmental Health and Occupational Medicine
Abstract:	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.
Keywords:	Toxicology
Date:	2006-12
Relation:	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
Appears in Collections:	[Louis W. Chang(1999-2009)] Periodical Articles [Tsui-Chun Tsou] Periodical Articles

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