Department of Medical and Surgical Sciences (DIMEC), University of Bologna, S. Orsola-Malpighi Hospital, via Massarenti 9, Bologna, 40138, Italy.
Department of Medical and Surgical Sciences (DIMEC), and Health Sciences & Technologies Interdepartmental Center for Industrial Research (CIRI SDV), University of Bologna, S. Orsola-Malpighi Hospital, via Massarenti 9, Bologna, 40138, Italy.
Mol Cell Endocrinol. 2020 Sep 15;515:110922. doi: 10.1016/j.mce.2020.110922. Epub 2020 Jul 1.
Poly- and perfluoroalkyl substances (PFAS) are a class of endocrine disrupting chemicals (EDCs) reported to alter thyroid function. Iodide uptake by thyroid follicular cells, an early step in the synthesis of thyroid hormones, is a potential target for thyroid disruption by EDCs. The aim of the present study was to evaluate the acute effects of perfluorooctane sulfonic acid (PFOS) and perfluorooctane carboxylic acid (PFOA), two of the most abundant PFAS in the environment, on iodide transport by thyroid follicular cells in vitro. Dynamic changes in intracellular iodide concentration were monitored by live cell imaging using YFP-H148Q/I152, a genetically encoded fluorescent iodide biosensor. PFOS, but not PFOA, acutely and reversibly inhibited iodide accumulation by FRTL-5 thyrocytes, as well as by HEK-293 cells transiently expressing the Sodium Iodide Symporter (NIS). PFOS prevented NIS-mediated iodide uptake and reduced intracellular iodide concentration in iodide-containing cells, mimicking the effect of the NIS inhibitor perchlorate. PFOS did not affect iodide efflux from thyroid cells. The results of this study suggest that disruption of iodide homeostasis in thyroid cells may be a potential mechanism for anti-thyroid health effects of PFOS. The study also confirms the utility of the YFP-H148Q/I152 cell-based assay to screen environmental PFAS, and other EDCs, for anti-thyroid activity.
多氟和全氟烷基物质(PFAS)是一类内分泌干扰化学物质(EDCs),据报道会改变甲状腺功能。甲状腺滤泡细胞对碘的摄取是甲状腺激素合成的早期步骤,是 EDCs 破坏甲状腺的潜在靶点。本研究旨在评估全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)这两种环境中最丰富的 PFAS 之一对甲状腺滤泡细胞体外碘转运的急性影响。使用 YFP-H148Q/I152(一种遗传编码的荧光碘生物传感器)通过活细胞成像监测细胞内碘浓度的动态变化。PFOS 可急性且可逆地抑制 FRTL-5 甲状腺细胞以及瞬时表达钠碘转运体(NIS)的 HEK-293 细胞对碘的积累,但 PFOA 没有。PFOS 可阻止 NIS 介导的碘摄取并降低含碘细胞中的细胞内碘浓度,模仿 NIS 抑制剂高氯酸盐的作用。PFOS 不影响甲状腺细胞中碘的流出。这项研究的结果表明,甲状腺细胞中碘稳态的破坏可能是 PFOS 对甲状腺健康产生抗作用的潜在机制。该研究还证实了使用 YFP-H148Q/I152 基于细胞的测定法筛选环境 PFAS 和其他 EDC 对甲状腺活性的抗作用的实用性。