Toxicity pathways of lipid metabolic disorders induced by typical replacement flame retardants via data-driven analysis, in silico and in vitro approaches
Wang, Xiaoqing1,2,4; Wang, Li3; Li, Fei1,2,5; Teng, Yuefa1,2,4; Ji, Chenglong1,2,5; Wu, Huifeng1,2,5
Source PublicationCHEMOSPHERE
ISSN0045-6535
2022
Volume287Pages:9
KeywordToxicity pathways Lipid metabolism disorder Bibliometric analysis Computational toxicology Data-driven analysis
DOI10.1016/j.chemosphere.2021.132419
Corresponding AuthorLi, Fei(fli@yic.ac.cn) ; Wu, Huifeng(hfwu@yic.ac.cn)
AbstractEndocrine-disrupting chemicals can interfere with hormone action via various pathways, thereby increasing the risk of adverse health outcomes. Organophosphorus ester (OPEs) retardants, a group of new emerging endocrine disruption chemicals, have been referred to as metabolism disruptors and reported to induce chronic health problems. However, the toxicity pathways were mainly focused on nuclear receptor signaling pathways. Significantly, the membrane receptor pathway (such as G protein-coupled estrogen receptor 1 (GPER) signaling pathway) had been gradually realized as the important role in respond more effective to lipid metabolism disorder than traditional nuclear receptors, whereas the detailed mechanism was unclear yet. Therefore, this study innovatively integrated the bibliometric analysis, in silico and in vitro approach to develop toxicity pathways for the mechanism interpretation. Bibliometric analysis found that the typical OPEs -triphenyl phosphate was a major concern of lipid metabolism abnormality. Results verified that TPP could damage the structures of cell membranes and exert an agonistic effect of GPER as the molecular initiating event. Then, the activated GPER could trigger the PI3K-Akt/NCOR1 and mTOR/S6K2/PPAR alpha transduction pathways as key event 1 (KE1) and affect the process of lipid metabolism and synthesis (CPT1A, CPT2, SREBF2 and SCD) as KE2. As a result, these alterations led to lipid accumulation as adverse effect at cellular-levels. Furthermore, the potential outcomes (such as immunity damage, weight change and steatohepatitis) at high biological levels were expanded. These findings improved knowledge to deeply understand toxicity pathways of phosphorus flame retardants and then provided a theoretical basis for risk assessments.
Funding OrganizationYantai Science and Technology Development Plan ; National Natural Science Founda-tion of China ; Youth Innovation Pro-motion Association CAS
Indexed BySCI
Language英语
WOS KeywordENDOCRINE-DISRUPTING CHEMICALS ; MOLECULAR-DYNAMICS ; GLOBAL TRENDS ; MEMBRANE ; DIPALMITOYLPHOSPHATIDYLCHOLINE ; BILAYER
WOS Research AreaEnvironmental Sciences & Ecology
WOS IDWOS:000704920000003
Citation statistics
Cited Times:9[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.yic.ac.cn/handle/133337/30785
Collection中国科学院海岸带环境过程与生态修复重点实验室
中国科学院海岸带环境过程与生态修复重点实验室_海岸带环境过程实验室
Corresponding AuthorLi, Fei; Wu, Huifeng
Affiliation1.Chinese Acad Sci, Yantai Inst Coastal Zone Res YIC, CAS Key Lab Coastal Environm Proc & Ecol Remediat, Yantai 264003, Peoples R China
2.YICCAS, Shandong Key Lab Coastal Environm Proc, Yantai 264003, Peoples R China
3.Yantai Yuhuangding Hosp, Dept Western Med, Yantai 264000, Shandong, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Ctr Ocean Megasci, Qingdao 266071, Peoples R China
Recommended Citation
GB/T 7714
Wang, Xiaoqing,Wang, Li,Li, Fei,et al. Toxicity pathways of lipid metabolic disorders induced by typical replacement flame retardants via data-driven analysis, in silico and in vitro approaches[J]. CHEMOSPHERE,2022,287:9.
APA Wang, Xiaoqing,Wang, Li,Li, Fei,Teng, Yuefa,Ji, Chenglong,&Wu, Huifeng.(2022).Toxicity pathways of lipid metabolic disorders induced by typical replacement flame retardants via data-driven analysis, in silico and in vitro approaches.CHEMOSPHERE,287,9.
MLA Wang, Xiaoqing,et al."Toxicity pathways of lipid metabolic disorders induced by typical replacement flame retardants via data-driven analysis, in silico and in vitro approaches".CHEMOSPHERE 287(2022):9.
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