Binding of common organic UV-filters to the thyroid hormone transport protein transthyretin using in vitro and in silico studies: potential implications in health

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• dc.contributor.author Cotrina, Ellen
• dc.contributor.author Oliveira, Ângela
• dc.contributor.author Llop, Jordi
• dc.contributor.author Quintana, Jordi
• dc.contributor.author Biarnés, Xevi
• dc.contributor.author Cardoso, Isabel
• dc.contributor.author Díaz-Cruz, M. Silvia
• dc.contributor.author Arsequell, Gemma
• dc.date.accessioned 2023-03-13T11:45:24Z
• dc.date.available 2023-03-13T11:45:24Z
• dc.date.issued 2023
• dc.description Includes supplementary materials for the online appendix.
• dc.description.abstract Several anthropogenic contaminants have been identified as competing with the thyroid hormone thyroxine (T4) for binding to transport proteins as transthyretin (TTR). This binding can potentially create toxicity mechanisms posing a threat to human health. Many organic UV filters (UVFs) and paraben preservatives (PBs), widely used in personal care products, are chemicals of emerging concern due to their adverse effects as potential thyroid-disrupting compounds. Recently, organic UVFs have been found in paired maternal and fetal samples and PBs have been detected in placenta, which opens the possibility of the involvement of TTR in the transfer of these chemicals across physiological barriers. We aimed to investigate a discrete set of organic UVFs and PBs to identify novel TTR binders. The binding affinities of target UVFs towards TTR were evaluated using in vitro T4 competitive binding assays. The ligand-TTR affinities were determined by isothermal titration calorimetry (ITC) and compared with known TTR ligands. In parallel, computational studies were used to predict the 3-D structures of the binding modes of these chemicals to TTR. Some organic UVFs, compounds 2,2',4,4'-tetrahydroxybenzophenone (BP2, Kd = 0.43 μM); 2,4-dihydroxybenzophenone (BP1, Kd = 0.60 μM); 4,4'-dihydroxybenzophenone (4DHB, Kd = 0.83 μM), and 4-hydroxybenzophenone (4HB, Kd = 0.93 μM), were found to display a high affinity to TTR, being BP2 the strongest TTR binder (ΔH = -14.93 Kcal/mol). Finally, a correlation was found between the experimental ITC data and the TTR-ligand docking scores obtained by computational studies. The approach integrating in vitro assays and in silico methods constituted a useful tool to find TTR binders among common organic UVFs. Further studies on the involvement of the transporter protein TTR in assisting the transplacental transfer of these chemicals across physiological barriers and the long-term consequences of prenatal exposure to them should be pursued.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cotrina EY, Oliveira Â, Llop J, Quintana J, Biarnés X, Cardoso I, et al. Binding of common organic UV-filters to the thyroid hormone transport protein transthyretin using in vitro and in silico studies: potential implications in health. Environmental Research. 2023 Jan 15;217:114836. DOI: 10.1016/j.envres.2022.114836
• dc.identifier.doi http://dx.doi.org/10.1016/j.envres.2022.114836
• dc.identifier.issn 0013-9351
• dc.identifier.uri http://hdl.handle.net/10230/56193
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Environmental Research. 2023 Jan 15;217:114836
• dc.rights © 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Endocrine disrupting compounds
• dc.subject.keyword Parabens
• dc.subject.keyword Sunscreens
• dc.subject.keyword Transplacental transport
• dc.subject.keyword Transthyretin mediated transport
• dc.subject.keyword Transthyretin-binders
• dc.subject.keyword UV-filters
• dc.title Binding of common organic UV-filters to the thyroid hormone transport protein transthyretin using in vitro and in silico studies: potential implications in health
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion