Li Jian, Xu Ying, Li Na, Zuo Rui, Zhai Yuanzheng, Chen Haiyang
Engineering Research Center of Groundwater Pollution Control and Remediation, Ministry of Education, College of Water Sciences, Beijing Normal University, Beijing 100875, China.
Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Environ Sci Technol. 2022 Apr 5;56(7):4241-4250. doi: 10.1021/acs.est.1c05956. Epub 2022 Mar 9.
Earlier mechanistic studies of many prohibited flame retardants (FRs) highlighted their thyroid hormone-disrupting activity through nuclear thyroid hormone receptors (nTRs), whereas some alternative FRs such as organophosphate esters (OPEs) exerted weak nTR-disrupting effects. However, an increasing number of studies have revealed that OPEs also exert thyroid hormone-disrupting effects, and the underlying mechanism is unclear. Herein, the thyroid hormone-disrupting effects and mechanisms of 8 typical OPEs were investigated using integrated , , and assays. All tested chemicals competitively bound to the membrane thyroid hormone receptor (mTR) [the 20% relative inhibitory concentration (RIC20): (3.5 ± 0.2) × 10 to (4.9 ± 1.0) × 10 nM], and Cl-OPEs and alkyl-OPEs had lower RIC20 values. In contrast, only 4 OPEs showed nTR antagonistic activities at higher concentrations [≥ (4.8 ± 0.8) × 10 nM]. Cl-OPEs and alkyl-OPEs preferentially interacted with mTR. Molecular docking illustrated that OPEs docked into mTRs, consistent with the competitive binding assay. analyses of zebrafish embryonic development confirmed that tris(1,3-dichloro-2-propyl) phosphate induced inappropriate expression of proteins, and these protein interactions might be associated with mTR according to the quantitative proteomic analysis. Based on the results, mTR might play a critical role in mediating the thyroid hormone-disrupting effects of OPEs.
早期对许多禁用阻燃剂（FRs）的机制研究强调了它们通过核甲状腺激素受体（nTRs）干扰甲状腺激素的活性，而一些替代阻燃剂，如有机磷酸酯（OPEs），对nTRs的干扰作用较弱。然而，越来越多的研究表明，OPEs也具有干扰甲状腺激素的作用，但其潜在机制尚不清楚。在此，我们使用综合的[此处原文缺失相关具体检测方法]检测方法，研究了8种典型OPEs的甲状腺激素干扰作用及其机制。所有测试化学品均与膜甲状腺激素受体（mTR）竞争性结合[20%相对抑制浓度（RIC20）：(3.5 ± 0.2) × 10至(4.9 ± 1.0) × 10 nM]，氯代OPEs和烷基OPEs的RIC20值较低。相比之下，只有4种OPEs在较高浓度[≥ (4.8 ± 0.8) × 10 nM]时表现出nTR拮抗活性。氯代OPEs和烷基OPEs优先与mTR相互作用。分子对接表明，OPEs与mTRs对接，这与竞争性结合试验结果一致。斑马鱼胚胎发育的[此处原文缺失相关具体分析内容]分析证实，磷酸三（1,3 - 二氯 - 2 - 丙基）酯诱导了蛋白质的异常表达，根据定量蛋白质组学分析，这些蛋白质相互作用可能与mTR有关。基于这些结果，mTR可能在介导OPEs的甲状腺激素干扰作用中起关键作用。
