Molecular mechanisms of human thyrocyte dysfunction induced by low concentrations of polychlorinated biphenyl 118 through the Akt/FoxO3a/NIS pathway

作者：Hongwei Guo, Hui Yang, Huanhuan Chen, Wen Li, Jinmei Tang, Pei Cheng, Yuchun Xie, Yun Liu, Guoxian Ding, Dai Cui, Xuqin Zheng, Yu Duan · 发表于：Journal of Applied Toxicology · 年份：2015 · DOI：10.1002/jat.3032 · 被引用次数：23 · 研究领域：FOXO transcription factor regulation、Toxic Organic Pollutants Impact、Environmental Toxicology and Ecotoxicology

Polychlorinated biphenyls (PCBs) are typical persistent organic pollutants that can interfere with multiple organ systems of humans. Previously, we concluded that persistent exposure to low doses of PCB118 could severely damage the thyroidal structure, dramatically decrease the concentration of serum thyroid hormones and inhibit the pivotal gene expressions such as sodium/iodide symporter (NIS) and thyroglobulin (Tg). To explore the molecular mechanisms of thyrocyte dysfunction induced by 2,3',4,4',5-pentachlorobiphenyl (PCB118), monolayer cultured human thyroid epithelial cells (HTECs) were treated with PCB118 or dimethyl sulfoxide (DMSO) as a control. Our results indicated that relatively higher concentrations of PCB118 could induce a loss in the viability of HTEC. In cultures with concentrations of PCB118 from 0.025 to 25 nM, which did not affect cell viability or apoptosis, concentrations of Tg and thyroxine (T(4)) were significantly decreased compared with those in the controls. In addition, mRNA and protein levels of Akt were increased significantly in the PCB118-treated groups, whereas FoxO3a expression did not show particular variation. Furthermore, exposure to PCB118 was associated with a significant increase of the protein levels of p-Akt and p-FoxO3a, and these effects were blocked by LY294002. In contrast, mRNA and protein expression levels of NIS were decreased significantly, and this effect was blocked by LY294002. Unlike control cells, a cytoplasmic shift of Fo...