Chlorinated Polyfluoroalkylether Sulfonates Exhibit Similar Binding Potency and Activity to Thyroid Hormone Transport Proteins and Nuclear Receptors as Perfluorooctanesulfonate

Chlorinated polyfluoroalkylether sulfonates (Cl-PFAESs) have been used as perfluorooctanesulfonate (PFOS) alternatives in the chrome plating industry for years. Although Cl-PFAESs have become ubiquitous environmental contaminants, knowledge on their toxicological mechanism remains very limited. We c...

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Bibliographic Details
Published inEnvironmental science & technology Vol. 52; no. 16; pp. 9412 - 9418
Main Authors Xin, Yan, Ren, Xiao-Min, Ruan, Ting, Li, Chuan-Hai, Guo, Liang-Hong, Jiang, Guibin
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 21.08.2018
Subjects
Activation
Affinity
Binding
Cell growth
Cell proliferation
Chemical activity
Chemicals
Chromium plating
Contaminants
Disruption
Fluorescence
Hormones
Molecular docking
Molecular dynamics
Nuclear receptors
Organic chemistry
Perfluorooctane sulfonic acid
Protein transport
Proteins
Receptors
Reporter gene
Sulfonates
Thyroid
Thyroid gland
Transport
Transthyretin
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Summary:Chlorinated polyfluoroalkylether sulfonates (Cl-PFAESs) have been used as perfluorooctanesulfonate (PFOS) alternatives in the chrome plating industry for years. Although Cl-PFAESs have become ubiquitous environmental contaminants, knowledge on their toxicological mechanism remains very limited. We compared potential thyroid hormone (TH) disruption effects of Cl-PFAESs and PFOS via the mechanisms of competitive binding to TH transport proteins and activation of TH receptors (TRs). Fluorescence binding assays revealed that 6:2 Cl-PFAES, 8:2 Cl-PFAES and F-53B (a mixture of 6:2 and 8:2 Cl-PFAES) all interacted with a TH transport protein transthyretin (TTR), with 6:2 Cl-PFAES showing the highest affinity. It was also found that the chemicals interacted with TRs, with the affinity following the order of 6:2 Cl-PFAES > PFOS > 8:2 Cl-PFAES. In reporter gene assays the chemicals exhibited agonistic activity toward TRs, with the potency of 6:2 Cl-PFAES comparable to that of PFOS. The chemicals also promoted GH3 cell proliferation, with 6:2 Cl-PFAES displaying the highest potency. Molecular docking and molecular dynamic simulation revealed that both Cl-PFAESs fit into the ligand binding pockets of TTR and TRs with the binding modes similar to PFOS. Collectively, our results demonstrate that Cl-PFAESs might cause TH disruption effects through competitive binding to transport proteins and activation of TRs.
ISSN:0013-936X
1520-5851
DOI:10.1021/acs.est.8b01494