Interaction of BDE-47 with nuclear receptors (NRs) based on the cytotoxicity: In vitro investigation and molecular interaction
文献类型：期刊论文
| 作者 | Song, Jiayi; Li, Yunxiu; Zhao, Chunyan; Zhou, Qunfang; Zhang, Jianqing |
| 刊名 | ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
 |
| 出版日期 | 2021-01-15 |
| 卷号 | 208页码:- |
| ISSN号 | 0147-6513 |
| 关键词 | BDE-47 Nuclear receptors Molecular simulation RXR alpha Cytotoxicity |
| 英文摘要 | Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting chemicals that possess neuroendocrine and reproductive toxicity to humans and disturb thyroid hormone homeostasis, neurobehavior, and development. The most predominant congener of PBDEs in humans and other organisms is 2,2 ',4,4 '-tetrabromodiphenyl ether (BDE-47); however, the molecular mechanisms underlying its cytotoxicity remain largely unknown. Here, we evaluated the toxic effect and underlying mechanism of nuclear receptors (NRs) induced by BDE-47 in SK-N-SH human neuroblastoma cells. The CCK-8 cell viability assay showed that the proliferation of human SK-N-SH cells exposed to BDE-47 was significantly inhibited in timeand dose-dependent manners, and flow cytometry showed that cell cycle was arrested at the S phase after BDE-47 exposure. Moreover, compared with the control group, the expression of retinoic acid receptor alpha (RXR alpha), pregnane X receptor (PXR), thyroid hormone receptors (TRs), and peroxisome proliferator-activated receptors (PPARs) at the mRNA and protein levels was significantly increased, as determined by quantitative PCR and western blot analysis, demonstrating that BDE-47 activated the NRs in vitro. Moreover, BDE-47 could bind to all four NRs in the affinity order of PPAR gamma > PXR > TR beta > RXR alpha under molecular dynamics. Because RXR is the promiscuous dimerization partner for a large number of NRs, ZDock was used to calculate its interaction with other three NRs. Taking the number of hydrogen bonds and ZDock scores into account, the rank of docking ability between RXR alpha and the NRs was PXR > TR beta > PPAR gamma. Further analysis of the interaction between BDE-47 and dimerized-NRs, the affinity order was RXR alpha > TR beta > PXR > PPAR gamma via Glide. The results of this study demonstrated that BDE-47 interfered the cross-talk among NRs, especially the promiscuous RXR alpha, which might be critical for the harmonized re-adjustment of cytotoxicity and biological regulation. Our findings provide a better understanding of the mechanisms underlying toxic effects and intermolecular interaction induced by BDE-47. |
| WOS研究方向 | Environmental Sciences ; Toxicology |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/45760]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 作者单位 | 1.Shenzhen Ctr Dis Control & Prevent, POPs Lab, Shenzhen 518055, Peoples R China 2.Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China 3.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China |
| 推荐引用方式 GB/T 7714 | Song, Jiayi,Li, Yunxiu,Zhao, Chunyan,et al. Interaction of BDE-47 with nuclear receptors (NRs) based on the cytotoxicity: In vitro investigation and molecular interaction[J]. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,2021,208:-. |
| APA | Song, Jiayi,Li, Yunxiu,Zhao, Chunyan,Zhou, Qunfang,&Zhang, Jianqing.(2021).Interaction of BDE-47 with nuclear receptors (NRs) based on the cytotoxicity: In vitro investigation and molecular interaction.ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,208,-. |
| MLA | Song, Jiayi,et al."Interaction of BDE-47 with nuclear receptors (NRs) based on the cytotoxicity: In vitro investigation and molecular interaction".ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 208(2021):-. |
入库方式： OAI收割
来源：生态环境研究中心
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