https://scholars.lib.ntu.edu.tw/handle/123456789/544330
標題: | Antagonistic effect of N-ethylmaleimide on arsenic-mediated oxidative stress-induced poly(ADP-ribosyl)ation and cytotoxicity | 作者: | Wang A.S.-S. Chou Y.-T. YEONG-SHIAU PU |
關鍵字: | arsenic; DNA damage; N-ethylmaleimide; PARP; poly(ADP-ribosyl)ation | 公開日期: | 2017 | 出版社: | John Wiley and Sons Ltd | 卷: | 37 | 期: | 5 | 起(迄)頁: | 573-582 | 來源出版物: | Journal of Applied Toxicology | 摘要: | Long-term exposure to arsenic has been known to induce neoplastic initiation and progression in several organs; however, the role of arsenic (As2O3) in oxidative stress-mediated DNA damage remains elusive. One of the immediate cellular responses to DNA damage is poly(ADP-ribosyl)ation (PARylation), which mediates DNA repair and enhances cell survival. In this study, we found that oxidative stress (H2O2)-induced PARylation was suppressed by As2O3 exposure in different human cancer cells. Moreover, As2O3 treatment promoted H2O2-induced DNA damage and apoptosis, leading to increased cell death. We found that N-ethylmaleimide (NEM), an organic compound derived from maleic acid, could reverse As2O3-mediated effects, thus enhancing PARylation with attenuated cell death and increased cell survival. Pharmacologic inhibition of glutathione with l-buthionine-sulfoximine blocked the antagonistic effect of NEM on As2O3, thereby continuing As2O3-mediated suppression of PARylation and causing DNA damage. Our findings identify NEM as a potential antidote against As2O3-mediated DNA damage in a glutathione-dependent manner. Copyright ? 2016 John Wiley & Sons, Ltd. Copyright ? 2016 John Wiley & Sons, Ltd. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84996602242&doi=10.1002%2fjat.3394&partnerID=40&md5=4bd68070806607f56f049c912abb1687 https://scholars.lib.ntu.edu.tw/handle/123456789/544330 |
ISSN: | 0260-437X | DOI: | 10.1002/jat.3394 | SDG/關鍵字: | arsenic; buthionine sulfoximine; glutathione; hydrogen peroxide; maleic acid; n ethylmaleimide; poly(adenosine diphosphate ribose); antidote; arsenic trioxide; buthionine sulfoximine; n ethylmaleimide; organoarsenic derivative; oxide; A-549 cell line; apoptosis; Article; bladder cancer; cell death; cell survival; cell viability; comet assay; controlled study; DNA strand breakage; down regulation; drug antagonism; drug cytotoxicity; flow cytometry; human; human cell; immunofluorescence; leukemia cell line; oxidative stress; priority journal; protein interaction; antagonists and inhibitors; CFU counting; DNA damage; DNA repair; drug effects; oxidative stress; poly(adenosine diphosphate) ribosylation; tumor cell line; Antidotes; Apoptosis; Arsenicals; Buthionine Sulfoximine; Cell Line, Tumor; Cell Survival; Colony-Forming Units Assay; Comet Assay; DNA Damage; DNA Repair; Ethylmaleimide; Humans; Oxidative Stress; Oxides; Poly ADP Ribosylation |
顯示於: | 醫學系 |
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