Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation
文献类型：期刊论文
| 作者 | Zhu, Liangliang1; Xiao, Ling1; Xia, Yangliu2; Zhou, Kun3; Wang, Huili1; Huang, Minyi1; Ge, Guangbo2; Wu, Yan1; Wu, Ganlin1; Yang, Ling2 |
| 刊名 | toxicology and applied pharmacology
 |
| 出版日期 | 2015-03-01 |
| 卷号 | 283期号:2页码:109-116 |
| 关键词 | Diethylstilbestrol UGT1A1 UGT1A4 Estradiol glucuronidation |
| 英文摘要 | this in vitro study investigates the effects of diethylstilbestrol (des), a widely used toxic synthetic estrogen, on estradiol-3- and 17-o- (e2-3/17-0) glucuronidation, via culturing human liver microsomes (hlms) or recombinant udp-glucuronosyltransferases (ugts) with des and e2. des can potently inhibit e2-3-o-glucuronidation in hlm, a probe reaction for ugt1a1. kinetic assays indicate that the inhibition follows a competitive inhibition mechanism, with the ki value of 2.1 +/- 03 mu m, which is less than the possible in vivo level. in contrast to the inhibition on e2-3-o-glucuronidation, the acceleration is observed on e2-17-o-glucuronidation in hlm, in which cholestatic e2-17-o-glucuronide is generated. in the presence of des (0-6.25 mu m), k-m values for e2-17-o-glucuronidation are located in the range of 7.2-7.4 mu m, while v-max values range from 0.38 to 1.54 nmol/min/mg. the mechanism behind the activation in hlm is further demonstrated by the fact that des can efficiently elevate the activity of ugt1a4 in catalyzing e2-17-o-glucuronidation. the presence of des (2 mu m) can elevate v-max from 0.016 to 0.81 nmol/min/mg, while lifting k-m in a much lesser extent from 4.4 to 11 mu m. activation of e2-17-o-glucuronidation is well described by a two binding site model, with k-a, alpha, and beta values of 0.077 +/- 0.18 mu m, 33 +/- 1.1 and 104 +/- 56, respectively. however, diverse effects of des towards e2-3/17-o-glucuronidation are not observed in liver microsomes from several common experimental animals. in summary, this study issues new potential toxic mechanisms for des: potently inhibiting the activity of ugt1a1 and powerfully accelerating the formation of cholestatic e2-17-o-glucuronide by ugt1a4. (c) 2015 elsevier inc. all rights reserved. |
| WOS标题词 | science & technology ; life sciences & biomedicine |
| 类目[WOS] | pharmacology & pharmacy ; toxicology |
| 研究领域[WOS] | pharmacology & pharmacy ; toxicology |
| 关键词[WOS] | glucuronosyltransferase ugt 1a4 ; hepatic drug glucuronidation ; messenger-rna expression ; udp-glucuronosyltransferases ; human liver ; genetic-polymorphism ; breast-cancer ; metabolism ; 17-beta-estradiol ; cytochrome-p450 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000350008300005 |
| 公开日期 | 2016-05-09 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/145938]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Anqing Normal Univ, Sch Life Sci, Ctr Drug & Food Safety Evaluat, Anqing 246011, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China 3.Liaoning Univ Tradit Chinese Med, Coll Pharm, Dalian 116600, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhu, Liangliang,Xiao, Ling,Xia, Yangliu,et al. Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation[J]. toxicology and applied pharmacology,2015,283(2):109-116. |
| APA | Zhu, Liangliang.,Xiao, Ling.,Xia, Yangliu.,Zhou, Kun.,Wang, Huili.,...&Yang, Ling.(2015).Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation.toxicology and applied pharmacology,283(2),109-116. |
| MLA | Zhu, Liangliang,et al."Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation".toxicology and applied pharmacology 283.2(2015):109-116. |
入库方式： OAI收割
来源：大连化学物理研究所
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