title: Molecular mechanisms of human thyrocyte dysfunction induced by low concentrations of polychlorinated biphenyl 118 through the Akt/FoxO3a/NIS pathway.
abstract: 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 FoxO3a was observed in the PCB118-treated group. Our research suggests that PCB118 may induce thyrocyte dysfunction through the Akt/FoxO3a/NIS signalling pathway, which provides potential new insights for finding interventions to counteract the damage to the human body caused by PCBs.
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Hongwei
authors: H
authors: Guo
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Hui
authors: H
authors: Yang
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Huanhuan
authors: H
authors: Chen
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Wen
authors: W
authors: Li
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Jinmei
authors: J
authors: Tang
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Pei
authors: P
authors: Cheng
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Yuchun
authors: Y
authors: Xie
authors: Department of Gerontology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Yun
authors: Y
authors: Liu
authors: Department of Gerontology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Guoxian
authors: G
authors: Ding
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Dai
authors: D
authors: Cui
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Xuqin
authors: X
authors: Zheng
authors: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.
authors: Yu
authors: Y
authors: Duan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D027981:Symporters / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D000099209:Sodium-Iodide Symporters
chemical_list: D004785:Environmental Pollutants; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D011078:Polychlorinated Biphenyls; D051057:Proto-Oncogene Proteins c-akt; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C499517:FOXO3 protein, human; C070055:2,3',4,4',5-pentachlorobiphenyl
keywords: FoxO3a; NIS; PI3K/Akt; Polychlorinated biphenyls 118; thyrocyte dysfunction