Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada.
School of the Environment, University of Toronto, Toronto, ON M5S 3H6, Canada.
Environ Sci Technol. 2024 Jun 11;58(23):10227-10239. doi: 10.1021/acs.est.3c10973. Epub 2024 May 30.
Incidences of thyroid disease, which has long been hypothesized to be partially caused by exposure to thyroid hormone disrupting chemicals (TDCs), have rapidly increased in recent years. However, known TDCs can only explain a small portion (∼1%) of human transthyretin (hTTR) binding activities in environmental samples, indicating the existence of unknown hTTR ligands. In this study, we aimed to identify the major environmental hTTR ligands by employing protein ffinity urification with ontargeted nalysis (APNA). hTTR binding activities were detected in all 11 indoor dust and 9 out of 10 sewage sludge samples by the FITC-T displacement assay. By using APNA, 31 putative hTTR ligands were detected including perfluorooctanesulfonate (PFOS). Two of the most abundant ligands were identified as hydrocarbon surfactants ( dodecyl benzenesulfonate). Moreover, another abundant ligand was surprisingly identified as a disulfonate fluorescent brightener, 4,4'-bis(2-sulfostyryl)biphenyl sodium (CBS). CBS was validated as a nM-affinity hTTR ligand with an IC of 345 nM. In total, hydrocarbon surfactants and fluorescent brighteners explain 1.92-17.0 and 5.74-54.3% of hTTR binding activities in dust and sludge samples, respectively, whereas PFOS only contributed <0.0001%. Our study revealed for the first time that hydrocarbon sulfonates are previously overlooked hTTR ligands in the environment.
近年来，甲状腺疾病的发病率迅速上升，这种疾病长期以来一直被认为部分是由于暴露于甲状腺激素干扰化学物质（TDCs）所致。然而，已知的 TDC 只能解释环境样本中人类转甲状腺素蛋白（hTTR）结合活性的一小部分（约 1%），这表明存在未知的 hTTR 配体。在这项研究中，我们旨在通过使用靶向分析的蛋白质亲和力纯化（APNA）来鉴定主要的环境 hTTR 配体。通过 FITC-T 置换测定，在所有 11 个室内灰尘样本和 10 个污水污泥样本中的 9 个样本中检测到 hTTR 结合活性。通过 APNA，检测到 31 种可能的 hTTR 配体，包括全氟辛烷磺酸（PFOS）。两种最丰富的配体被鉴定为烃基表面活性剂（十二烷基苯磺酸钠）。此外，令人惊讶的是，另一种丰富的配体被鉴定为二磺酸盐荧光增白剂，4,4'-双（2-磺酰基）联苯钠盐（CBS）。CBS 被验证为具有 345 nM IC 的 nM 亲和力 hTTR 配体。总的来说，烃基表面活性剂和荧光增白剂分别解释了灰尘和污泥样本中 hTTR 结合活性的 1.92-17.0%和 5.74-54.3%，而 PFOS 的贡献<0.0001%。我们的研究首次揭示了烃基磺酸盐是环境中以前被忽视的 hTTR 配体。
