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Nongenomic effects and mechanistic study of butyl benzyl phthalate-induced thyroid disruption: Based on integrated in vitro, in silico assays and proteome analysis
Li, Jian; Xu, Ying; Jiang, Yuhao; Li, Na; Li, Zhanjie; Kong, Dongdong; Guo, Xueru; Zhang, Junbo; Zuo, Rui
2022-08-25
Source PublicationSCIENCE OF THE TOTAL ENVIRONMENT
ISSN0048-9697
Volume836Issue:0Pages:155715
AbstractBased on in vitro and in silico assays as well as proteome analysis, this study explored the nongcnomic mechanism for butyl benzyl phthalate (BBP)-induced thyroid disruption. Molecular docking simulations showed that BBP could dock into the Arg-Gly-Asp (RGD) domain of intcgrin alpha(v)beta(3) and form hydrogen bonds with a docking energy of -35.80 kcal/ mol. This chemical enhanced rat pituitary tumor cell (GH3) proliferation and exhibited thyroid hormone-disrupting effects at 5-10 mu mol/L. Meanwhile, BBP upregulated beta(3) gene expression and activated the downstream mitogcnactivated protein kinase (MAPK) pathway in GH3 cells. Interestingly, GH3 cell proliferation was attenuated by intcgrin alpha(v)beta(3) inhibitor (RGD peptide) or ERK1/2 inhibitor (PD98059), suggesting that the disruptions might be partly attributed to its interaction with integrin alpha(v)beta(3 )and activation of MAPK. Furthermore, quantitative proteomic analysis of zebrafish embryos exposed to BBP at an environmentally relevant concentration of 0.3 mu mol/L revealed that BBP perturbed proteins and pathways related to cell communication (e.g., integrin binding) and signal transduction (e.g., MAPK signaling pathway). Taken together, our results supported that the biological effects of BBP-activated integrin alpha(v)beta(3) mediated by the nongenomic pathway play an important role in its thyroid disruption. Capsule: The nongenomic pathway plays a vital role in the thyroid disruption-inducing actions of BBP.
Department中国科学院饮用水科学与技术重点实验室 ; 中国科学院饮用水科学与技术重点实验室
KeywordHORMONE CELLS RECEPTOR ALPHA(V)BETA(3) PROLIFERATION ACTIVATION TOXICITY EXPOSURE GROWTH ESTERS
Document Type期刊论文
Identifierhttps://ir.rcees.ac.cn/handle/311016/47881
Collection中国科学院饮用水科学与技术重点实验室
Corresponding AuthorZuo, Rui
Affiliation1.Beijing Normal Univ, Coll Water Sci, Engn Res Ctr Groundwater Pollut Control & Remedia, Minist Educ, Beijing 100875, Peoples R China
2.Beijing Normal Univ, Coll Chem, Key Lab Radiopharmaceut, Minist Educ, Beijing 100875, Peoples R China
3.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, Key Lab Drinking Water Sci & Technol, Beijing 100085, Peoples R China
Recommended Citation
GB/T 7714
Li, Jian,Xu, Ying,Jiang, Yuhao,et al. Nongenomic effects and mechanistic study of butyl benzyl phthalate-induced thyroid disruption: Based on integrated in vitro, in silico assays and proteome analysis[J]. SCIENCE OF THE TOTAL ENVIRONMENT,2022,836(0):155715.
APA Li, Jian.,Xu, Ying.,Jiang, Yuhao.,Li, Na.,Li, Zhanjie.,...&Zuo, Rui.(2022).Nongenomic effects and mechanistic study of butyl benzyl phthalate-induced thyroid disruption: Based on integrated in vitro, in silico assays and proteome analysis.SCIENCE OF THE TOTAL ENVIRONMENT,836(0),155715.
MLA Li, Jian,et al."Nongenomic effects and mechanistic study of butyl benzyl phthalate-induced thyroid disruption: Based on integrated in vitro, in silico assays and proteome analysis".SCIENCE OF THE TOTAL ENVIRONMENT 836.0(2022):155715.
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