Grupo de Pesquisa, Desenvolvimento e Inovação em Endocrinologia Experimental-GPDIEEx, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil, Av. Carlos Chagas Filho, 373; Bloco G- Sala G1-060 - Ilha do Fundão, Rio de Janeiro, RJ, 21941-912, Brazil.
Pós-graduação em Endocrinologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Environ Sci Pollut Res Int. 2018 Sep;25(27):26916-26926. doi: 10.1007/s11356-018-2419-y. Epub 2018 Jul 13.
Bisphenol A (BPA) is a well-known endocrine disruptor with several effects on reproduction, development, and cancer incidence, and it is highly used in the plastic industry. Bisphenol S (BPS) was proposed as an alternative to BPA since it has a similar structure and can be used to manufacture the same products. Some reports show that BPA interferes with thyroid function, but little is known about the involvement of BPS in thyroid function or how these molecules could possibly modulate at the same time the principal genes involved in thyroid physiology. Thus, the aims of this work were to evaluate in silico the possible interactions of BPA and BPS with the thyroid transcription factors Pax 8 and TTF1 and to study the actions in vivo of these compounds in zebrafish thyroid gene expression. Adult zebrafish treated with BPA or BPS showed that sodium iodide symporter, thyroglobulin, and thyroperoxidase genes were negatively or positively regulated, depending on the dose of the exposure. Human Pax 8 alignment with zebrafish Pax 8 and Rattus norvegicus TTF1 alignment with zebrafish TTF1 displayed highly conserved regions in the DNA binding sites. Molecular docking revealed the in silico interactions between the protein targets Pax 8 and TTF1 with BPA and BPS. Importance of some amino acids residues is highlighted and ratified by literature. There were no differences between the mean energy values for BPA docking in Pax 8 or TTF1. However, BPS energy values were lower in TTF1 docking compared to Pax 8 values. The number of amino acids on the protein interface was important for Pax 8 but not for TTF1. The main BPA interactions with proteins occurred through Van der Waals forces and pi-alkyl and alkyl interactions, while BPS interactions mainly occurred through carbon hydrogen bonds and conventional hydrogen bonds in addition to Van der Waals forces and pi-alkyl interactions. These data point to a possible interaction of BPA and BPS with Pax 8 and TTF1.
双酚 A（BPA）是一种众所周知的内分泌干扰物，对生殖、发育和癌症发病率有多种影响，并且在塑料行业中大量使用。双酚 S（BPS）被提议作为 BPA 的替代品，因为它具有相似的结构，可以用于制造相同的产品。一些报告表明 BPA 会干扰甲状腺功能，但对于 BPS 如何参与甲状腺功能或这些分子如何可能同时调节涉及甲状腺生理学的主要基因知之甚少。因此，这项工作的目的是评估 BPA 和 BPS 与甲状腺转录因子 Pax 8 和 TTF1 的可能相互作用，并研究这些化合物在斑马鱼甲状腺基因表达中的体内作用。用 BPA 或 BPS 处理的成年斑马鱼显示，钠碘转运体、甲状腺球蛋白和甲状腺过氧化物酶基因根据暴露剂量受到负调控或正调控。人类 Pax 8 与斑马鱼 Pax 8 的比对和大鼠 TTF1 与斑马鱼 TTF1 的比对显示 DNA 结合位点高度保守。分子对接显示了蛋白质靶标 Pax 8 和 TTF1 与 BPA 和 BPS 的体内相互作用。一些氨基酸残基的重要性被突出并得到文献的证实。BPA 在 Pax 8 或 TTF1 中的对接平均能量值没有差异。然而，与 Pax 8 值相比，BPS 在 TTF1 对接中的能量值较低。蛋白质界面上的氨基酸数量对 Pax 8 很重要，但对 TTF1 不重要。BPA 与蛋白质的主要相互作用是通过范德华力和 pi-烷基和烷基相互作用发生的，而 BPS 相互作用主要是通过碳氢键和除范德华力和 pi-烷基相互作用外的常规氢键发生的。这些数据表明 BPA 和 BPS 可能与 Pax 8 和 TTF1 相互作用。
