2,2 ',4,4 '-Tetrabromodiphenyl Ether (PBDE 47) Selectively Stimulates Proatherogenic PPAR gamma Signatures in Human THP-1 Macrophages to Contribute to Foam Cell Formation
文献类型：期刊论文
| 作者 | Ren, Qidong; Xie, Xinni; Zhao, Chuanfang; Wen, Qing; Pan, Ruiying ; Du, Yuguo
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| 刊名 | CHEMICAL RESEARCH IN TOXICOLOGY
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| 出版日期 | 2022-06-20 |
| 卷号 | 35期号:6页码:1023-1035 |
| ISSN号 | 0893-228X |
| 关键词 | ACTIVATED-RECEPTOR-GAMMA BROMINATED FLAME RETARDANTS ACID-BINDING PROTEIN GENE-EXPRESSION LIGAND-BINDING DIPHENYL ETHERS INDOOR DUST EXPOSURE CD36 ACCUMULATION |
| 英文摘要 | 2,2',4,4'-Tetrabromodiphenyl ether (PBDE 47) is one of the most prominent PBDE congeners detected in the human body, suggesting that the potential health risks of PBDE 47 should be thoroughly considered. However, the cardiovascular toxicity of PBDE 47 remains poorly understood. Here, toxic outcomes of PBDE 47 in human THP-1 macrophages concerning foam cell formation, which play crucial roles in the occurrence and development of atherosclerosis, were elucidated. First, our results indicated that PBDE 47 affected the PPAR gamma pathway most efficiently in THP-1 macrophages by transcriptomic analysis. Second, the PPAR gamma target genes CD36 and FABP4, responsible for lipid uptake and accumulation in macrophages, were consistently upregulated both at transcriptional and translational levels in THP-1 macrophages upon PBDE 47. Unexpectedly, PBDE 47 failed to activate the PPAR gamma target gene LXR alpha and PPAR gamma-LXR alpha-ABCA1/G1 cascade, which is activated by the PPAR gamma full agonist rosiglitazone and enables cholesterol efflux in macrophages. Thus, coincident with the selective upregulation of the PPAR gamma target genes CD36 and FABP4, PBDE 47, distinct from rosiglitazone, functionally resulted in more lipid accumulation and oxLDL uptake in THP-1 macrophages through high-content analysis (HCA). Moreover, these effects were markedly abrogated by the addition of the PPAR gamma antagonist T0070907. Mechanistically, the structural basis of selective activation of PPAR gamma by PBDE 47 was explored by molecular docking and dynamics simulation, which indicated that PBDE 47 interacted with the PPAR gamma ligand binding domain (PPAR gamma-LBD) distinctively from that of rosiglitazone. PBDE 47 was revealed to interact with helix 3 and helix 5 but not helix 12 in the PPAR gamma-LBD. Collectively, these results unraveled the potential cardiovascular toxicity of PBDE 47 by selective activation of PPAR gamma to facilitate foam cell formation for the first time. |
| 源URL | [https://ir.rcees.ac.cn/handle/311016/47446]  |
| 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.Univ Chinese Acad Sci, Coll Resources & Environm, Beijing 100049, Peoples R China 2.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 | Ren, Qidong,Xie, Xinni,Zhao, Chuanfang,et al. 2,2 ',4,4 '-Tetrabromodiphenyl Ether (PBDE 47) Selectively Stimulates Proatherogenic PPAR gamma Signatures in Human THP-1 Macrophages to Contribute to Foam Cell Formation[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2022,35(6):1023-1035. |
| APA | Ren, Qidong,Xie, Xinni,Zhao, Chuanfang,Wen, Qing,Pan, Ruiying,&Du, Yuguo.(2022).2,2 ',4,4 '-Tetrabromodiphenyl Ether (PBDE 47) Selectively Stimulates Proatherogenic PPAR gamma Signatures in Human THP-1 Macrophages to Contribute to Foam Cell Formation.CHEMICAL RESEARCH IN TOXICOLOGY,35(6),1023-1035. |
| MLA | Ren, Qidong,et al."2,2 ',4,4 '-Tetrabromodiphenyl Ether (PBDE 47) Selectively Stimulates Proatherogenic PPAR gamma Signatures in Human THP-1 Macrophages to Contribute to Foam Cell Formation".CHEMICAL RESEARCH IN TOXICOLOGY 35.6(2022):1023-1035. |
入库方式： OAI收割
来源：生态环境研究中心
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