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Optimized methods for measuring competitive binding of chemical substances to thyroid hormone distributor proteins transthyretin and thyroxine binding globulin.
Shen, Yang; Bovee, Toine F H; Molenaar, Douwe; Weide, Yoran; Nolles, Antsje; Braucic Mitrovic, Carmen; van Leeuwen, Stefan P J; Louisse, Jochem; Hamers, Timo.
Afiliação
  • Shen Y; Wageningen Food Safety Research (WFSR), Wageningen University and Research, Akkermaalsbos 2, 6708 WB, Wageningen, The Netherlands.
  • Bovee TFH; Wageningen Food Safety Research (WFSR), Wageningen University and Research, Akkermaalsbos 2, 6708 WB, Wageningen, The Netherlands. toine.bovee@wur.nl.
  • Molenaar D; Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
  • Weide Y; Wageningen Food Safety Research (WFSR), Wageningen University and Research, Akkermaalsbos 2, 6708 WB, Wageningen, The Netherlands.
  • Nolles A; Wageningen Food Safety Research (WFSR), Wageningen University and Research, Akkermaalsbos 2, 6708 WB, Wageningen, The Netherlands.
  • Braucic Mitrovic C; Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
  • van Leeuwen SPJ; Wageningen Food Safety Research (WFSR), Wageningen University and Research, Akkermaalsbos 2, 6708 WB, Wageningen, The Netherlands.
  • Louisse J; Wageningen Food Safety Research (WFSR), Wageningen University and Research, Akkermaalsbos 2, 6708 WB, Wageningen, The Netherlands.
  • Hamers T; European Food Safety Authority (EFSA), Parma, Italy.
Arch Toxicol ; 2024 Aug 21.
Article em En | MEDLINE | ID: mdl-39167138
ABSTRACT
Transthyretin (TTR) and thyroxine-binding globulin (TBG) are two major thyroid hormone (TH) distributor proteins in human plasma, playing important roles in stabilizing the TH levels in plasma, delivery of TH to target tissues, and trans-barrier transport. Binding of xenobiotics to these distributor proteins can potentially affect all these three important roles of distributor proteins. Therefore, fast and cost-effective experimental methods are required for both TTR and TBG to screen both existing and new chemicals for their potential binding. In the present study, the TTR-binding assay was therefore simplified, optimized and pre-validated, while a new TBG-binding assay was developed based on fluorescence polarization as a readout. Seven model compounds (including positive and negative controls) were tested in the pre-validation study of the optimized TTR-binding assay and in the newly developed TBG-binding assay. The dissociation constants of the natural ligand (thyroxine, T4) and potential competitors were determined and compared between two distributor proteins, showing striking differences for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA).
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Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Arch Toxicol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Arch Toxicol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda