New insights for the risk of bisphenol A: Inhibition of UDP-glucuronosyltransferases (UGTs)
New insights for the risk of bisphenol A: Inhibition of UDP-glucuronosyltransferases (UGTs)
复制标题
关于双酚 A 风险的新见解：抑制 UDP-葡萄糖醛酸基转移酶 (UGT)。
DOI：
10.1016/j.chemosphere.2013.06.070
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发表时间：
2013-10-01
期刊：
影响因子：
8.8
通讯作者：
Liu, Ren-Jie
中科院分区：
文献类型：
--
作者：
Jiang, Hua-Mao;Fang, Zhong-Ze;Liu, Ren-Jie
双酚A（BPA）是一种重要的内分泌干扰物，具有多种毒性。本研究旨在通过评价双酚A对尿苷二磷酸葡萄糖醛酸基转移酶（UGT）异构体的抑制作用来了解双酚A的毒性行为。采用体外重组UGT催化的4-甲基伞形酮（4-MU）葡萄糖醛酸化反应作为所有检测的UGT亚型的探针反应。结果表明，双酚A对UGT 2B亚型的抑制作用强于UGT 1A亚型。此外，测定了双酚A对UGT 2B 4、2B 7、2B 15和2B 17的抑制动力学类型和参数（Ki）。双酚A对UGT 2B 4具有竞争性抑制作用，对UGT 2B 7、2B 15和2B 17具有非竞争性抑制作用。UGT 2B 4、2B 7、2B 15和2B 17的抑制动力学参数（Ki）计算值分别为1.1、32.6、5.6和19.9 μ M。结合双酚A的体内浓度，预测UGT 2B 4、2B 7、2B 15和2B 17的暴露剂量升高分别增加29.1%、1%、5.7%和1.6%，表明双酚A对体内UGT 2B异构体介导的外源性物质和内源性物质代谢具有高度影响。这些数据为深入了解双酚A的毒理学提供了支持信息。(C)2013爱思唯尔有限公司保留所有权利。
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.