ATM/ATR-related checkpoint signals mediate arsenite-induced G2/M arrest in primary aortic endothelial cells

Archives of Toxicology
Tsui-Chun TsouLouis W Chang

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 G2/M phase arrest induced by arsenite. Our study revealed that lower concentrations of arsenite (1 and 3 microM) increased cell proliferation, whereas higher concentrations of arsenite (10, 20, and 30 microM) inhibited cell proliferation together with correlated increases in G2/M phase arrest. We found that this arsenite-induced G2/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-microM arsenite-induced G2/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 ...Continue Reading

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Citations

Jul 24, 2008·Archives of Toxicology·J G Hengstler, H M Bolt
Nov 14, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Keiko NoharaTakahiro Kobayashi
Jan 15, 2013·Environment International·Pritha BhattacharjeeAshok K Giri
Feb 13, 2007·Toxicology and Applied Pharmacology·Katsura SuzukiMasato Matsuoka
Jul 31, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kazuyuki OkamuraKeiko Nohara
Feb 11, 2014·The American Journal of Pathology·Robert H JenkinsDonald J Fraser
Jan 11, 2018·Science Signaling·Ji-Hoon LeeTanya T Paull
Oct 29, 2020·Technology in Cancer Research & Treatment·Ruifeng XunXianwang Wang
Aug 26, 2010·Chemical Research in Toxicology·Jong-Hang ChenChin-Cheng Chou
Nov 11, 2008·Archives of Biochemistry and Biophysics·Geetha M Habib

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