| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Guo, Hongwei Yang, Hui Chen, Huanhuan Li, Wen Tang, Jinmei Cheng, Pei Xie, Yuchun Liu, Yun Ding, Guoxian Cui, Dai Zheng, Xuqin Duan, Yu |
| Description |
Country affiliation: China Author Affiliation: Guo H ( Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Yang H ( Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Chen H ( Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Li W ( Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Tang J ( Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Cheng P ( Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Xie Y ( Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Liu Y ( Department of Gerontology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Ding G ( Department of Gerontology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Cui D ( Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Zheng X ( Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.); Duan Y ( Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.) |
| 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. Copyright © 2015 John Wiley & Sons, Ltd. |
| File Format |
HTM / HTML |
| ISSN |
0260437X |
| Issue Number |
9 |
| Volume Number |
35 |
| e-ISSN |
10991263 |
| Journal |
Journal of Applied Toxicology |
| Language |
English |
| Publisher |
Wiley |
| Publisher Date |
2015-09-01 |
| Publisher Place |
Great Britain (UK) |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Discipline Toxicology Environmental Pollutants Toxicity Forkhead Transcription Factors Metabolism Polychlorinated Biphenyls Proto-oncogene Proteins C-akt Symporters Thyroid Gland Drug Effects Apoptosis Blotting, Western Cell Survival Cells, Cultured Epithelial Cells Enzymology Pathology Humans Primary Cell Culture Real-time Polymerase Chain Reaction Signal Transduction Journal Article Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Toxicology |
