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题名: New insights for the risk of bisphenol A: Inhibition of UDP-glucuronosyltransferases (UGTs)
作者: Jiang, Hua-Mao1;  Fang, Zhong-Ze1, 2, 3, 4;  Cao, Yun-Feng2, 3;  Hu, Cui-Min1, 6;  Sun, Xiao-Yu2, 3;  Hong, Mo2, 3;  Yang, Ling5;  Ge, Guang-Bo5;  Liu, Yong5;  Zhang, Yan-Yan2, 3;  Dong, Qiang1;  Liu, Ren-Jie1
关键词: Bisphenol A ;  UDP-glucuronosyltransferase (UGT) ;  Risk evaluation ;  Recombinant enzymes
刊名: CHEMOSPHERE
发表日期: 2013-10-01
DOI: 10.1016/j.chemosphere.2013.06.070
卷: 93, 期:6, 页:1189-1193
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Environmental Sciences
研究领域[WOS]: Environmental Sciences & Ecology
英文摘要: Bisphenol A (BPA), the important endocrine-disrupting chemical (EDC), has been reported to be able to induce various toxicity. The present study aims to understand the toxicity behavior of bisphenol A through evaluating the inhibition profile of bisphenol A towards UDP-glucuronosyltransferase (UGT) isoforms. In vitro recombinant UGTs-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed as probe reaction for all the tested UGT isoforms. The results showed that bisphenol A exerted stronger inhibition towards UGT2B isoforms than UGT1A isoforms. Furthermore, the inhibition kinetic type and parameters (K-i) were determined for the inhibition of bisphenol A towards UGT2B4, 2B7, 2B15, and 2B17. Bisphenol A exhibited the competitive inhibition towards UGT2B4, and noncompetitive inhibition towards UGT2B7, 2B15 and 2B17. The inhibition kinetic parameters (K-i) were calculated to be 1.1, 32.6, 5.6, and 19.9 mu M for UGT2B4, 2B7, 2B15 and 2B17, respectively. In combination with the in vivo concentration of bisphenol A, the elevation of exposure dose was predicted to increase by 29.1%, 1%, 5.7%, and 1.6% for UGT2B4, 2B7, 2B15, and 2B17, indicating the high influence of bisphenol A towards the in vivo UGT2B isofroms-mediated metabolism of xenobiotics and endogenous substances. All these data provide the supporting information for deeper understanding of toxicology of bisphenol A. (C) 2013 Elsevier Ltd. All rights reserved.
关键词[WOS]: GLUCURONIDATION ;  EXPOSURE ;  ISOFORMS ;  4-METHYLUMBELLIFERONE ;  POLYMORPHISM ;  ASSOCIATION ;  UGT2B7 ;  ENZYME ;  ACID ;  CITY
语种: 英语
WOS记录号: WOS:000326857900048
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/137835
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Liaoning Med Univ, Jinzhou, Liaoning, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian 116023, Peoples R China
3.Liaoning Med Univ, Affiliated Hosp 1, Dalian 116023, Peoples R China
4.NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA
5.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
6.Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20057 USA

Recommended Citation:
Jiang, Hua-Mao,Fang, Zhong-Ze,Cao, Yun-Feng,et al. New insights for the risk of bisphenol A: Inhibition of UDP-glucuronosyltransferases (UGTs)[J]. CHEMOSPHERE,2013,93(6):1189-1193.
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