Multiple bioanalytical methods reveal a thyroid-disrupting mechanism related to the membrane receptor integrin alpha(v)beta(3)
文献类型：期刊论文
| 作者 | Kong, Dongdong; Li, Jian; Li, Na ; Zhang, Shurong; Xu, Ying
|
| 刊名 | ENVIRONMENTAL POLLUTION
 |
| 出版日期 | 2021-06-15 |
| 卷号 | 279页码:- |
| 关键词 | DEHP Thyroid-disrupting effect Toxic mechanism Integrin alpha(v)beta(3) ERK1/2 |
| ISSN号 | 0269-7491 |
| 英文摘要 | Di(2-ethylhexyl) phthalate (DEHP), a manufactured chemical, is suitable for large-scale production and has extensive applications. Although restricted for use, DEHP is still ubiquitous in the environment and shows potential to disrupt the structure or function of the thyroid system. However, its toxic mechanism is complex and not clearly understood. In this study, a battery of methods was employed to investigate DEHP-induced thyroid-disrupting effects and their mechanism of action, focusing on a newly discovered membrane receptor-mediated mechanism. The results showed that DEHP promoted rat pituitary tumor (GH3) cell proliferation and c-fos gene expression at environment level concentrations (2 and 5 mmol/L) in a manner similar to that of the natural thyroid hormone 3,3',5-triiodo-L-thyronine (T3). The macromolecule DEHP-BSA cannot pass through the cell membrane to interact with nuclear receptors but upregulated the c-fos gene expression when administered at concentrations comparable to DEHP concentrations; molecular docking demonstrated that DEHP has affinity for the membrane receptor integrin alpha(v)beta(3); DEHP at 2 mmol/L upregulated the beta(3) gene expression in GH3 cells; after the addition of integrin alpha(v)beta(3)-inhibiting RGD peptide, DEHP-induced c-fos gene upregulation decreased. All of these findings support the supposition that DEHP-induced thyroid-disrupting effects might be mediated by the membrane receptor integrin alpha(v)beta(3). Moreover, DEHP activated the downstream extracellular regulated protein kinase (ERK1/2) pathway, upregulating the gene expression of raf-1, MEK-1 and MAPK1 and increasing the protein levels of p-ERK; interestingly, ERK1/2 activation and c-fos upregulation induced by DEHP were attenuated by PD98059 (an ERK1/2 inhibitor). Taken together, the data suggest that the membrane receptor integrin alpha(v)beta(3) and the downstream ERK1/2 pathway might be involved in DEHPinduced thyroid-disrupting effects. This study provides new insight into the thyroid-disrupting effect and the underlying mechanism and will advance the effort to construct adverse outcome pathways of DEHP and other thyroid hormone disrupting chemicals. (c) 2021 Elsevier Ltd. All rights reserved. |
| WOS研究方向 | Environmental Sciences |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/46239]  |
| 专题 | 生态环境研究中心_中国科学院饮用水科学与技术重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, Key Lab Drinking Water Sci & Technol, Beijing 100085, Peoples R China 2.Beijing Normal Univ, Coll Water Sci, Engn Res Ctr Groundwater Pollut Control & Remedia, Minist Educ, Beijing 100875, Peoples R China |
| 推荐引用方式 GB/T 7714 | Kong, Dongdong,Li, Jian,Li, Na,et al. Multiple bioanalytical methods reveal a thyroid-disrupting mechanism related to the membrane receptor integrin alpha(v)beta(3)[J]. ENVIRONMENTAL POLLUTION,2021,279:-. |
| APA | Kong, Dongdong,Li, Jian,Li, Na,Zhang, Shurong,&Xu, Ying.(2021).Multiple bioanalytical methods reveal a thyroid-disrupting mechanism related to the membrane receptor integrin alpha(v)beta(3).ENVIRONMENTAL POLLUTION,279,-. |
| MLA | Kong, Dongdong,et al."Multiple bioanalytical methods reveal a thyroid-disrupting mechanism related to the membrane receptor integrin alpha(v)beta(3)".ENVIRONMENTAL POLLUTION 279(2021):-. |
入库方式： OAI收割
来源：生态环境研究中心
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