College of Environmental and Resource Sciences , Zhejiang University , Hangzhou 310058 , 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. 2018 Jun 5;52(11):6617-6625. doi: 10.1021/acs.est.8b00776. Epub 2018 May 24.
Bisphenol S (4-hydroxyphenyl sulfone, BPS) is increasingly used as a bisphenol A (BPA) alternative. The global usage of BPS and its analogues (BPSs) resulted in the frequent detection of their residues in multiple environmental media. We investigated their potential endocrine-disrupting effects toward thyroid hormone receptor (TR) β. The molecular interaction of BPSs toward TRβ ligand binding domain (LBD) was probed by fluorescence spectroscopy and molecular dynamics (MD) simulations. BPSs caused the static fluorescence quenching of TRβ LBD. The 100 ns MD simulations revealed that the binding of BPSs caused significant changes in the distance between residue His435 at helix 11(H11) and residue Phe459 at H12 in comparison to no ligand-bound TRβ LBD, indicating relative repositioning of H12. The recombinant two-hybrid yeast assay showed that tetrabromobisphenol S (TBBPS) and tetrabromobisphenol A (TBBPA) have potent antagonistic activity toward TRβ, with an IC of 10.1 and 21.1 nM, respectively. BPS and BPA have the antagonistic activity with IC of 312 and 884 nM, respectively. BPSs significantly altered the expression level of mRNA of TRβ gene in zebrafish embryos. BPS and TBBPS at environmentally relevant concentrations have antagonistic activity toward TRβ, implying that BPSs are not safe BPA alternatives in many BPA-free products. Future health risk assessments for TR disruption and other adverse effects should focus more on the structure-activity relationship in the design of environmentally benign BPA alternatives.
双酚 S（4-羟基二苯砜，BPS）作为双酚 A（BPA）的替代品，应用日益广泛。BPS 和其类似物（BPSs）在全球范围内的使用导致其残留物在多种环境介质中频繁被检出。我们研究了它们对甲状腺激素受体（TR）β的潜在内分泌干扰作用。通过荧光光谱法和分子动力学（MD）模拟研究了 BPSs 与 TRβ配体结合域（LBD）的分子相互作用。BPSs 导致 TRβ LBD 的静态荧光猝灭。100 ns MD 模拟表明，与无配体结合的 TRβ LBD 相比，BPSs 的结合导致 H11 上残基 His435 与 H12 上残基 Phe459 之间的距离发生显著变化，表明 H12 相对重新定位。重组双杂交酵母测定显示，四溴双酚 S（TBBPS）和四溴双酚 A（TBBPA）对 TRβ 具有很强的拮抗活性，IC 分别为 10.1 和 21.1 nM。BPS 和 BPA 的拮抗活性分别为 312 和 884 nM。BPSs 显著改变了斑马鱼胚胎中 TRβ 基因的 mRNA 表达水平。在环境相关浓度下，BPS 和 TBBPS 对 TRβ 具有拮抗活性，这表明在许多无 BPA 产品中，BPS 并不是安全的 BPA 替代品。未来的 TR 破坏和其他不良影响的健康风险评估应更多地关注环境友好型 BPA 替代品的结构-活性关系设计。
