Inhibition of the thyroid hormonogenic H 2 O 2 production by Duox/DuoxA in zebrafish reveals VAS2870 as a new goitrogenic compound.

Autor: Giusti N; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: Nicoletta.Giusti@ulb.ac.be., Gillotay P; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: Pierre.Gillotay@ulb.ac.be., Trubiroha A; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium; Present Address: German Federal Institute for Risk Assessment (BfR), Department Chemicals and Product Safety, Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany. Electronic address: achim.trubiroha@bfr.bund.de., Opitz R; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium; Institute of Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. Electronic address: robert.opitz@charite.de., Dumont JE; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: jedumont@ulb.ac.be., Costagliola S; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: scostag@ulb.ac.be., De Deken X; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: xdedeken@ulb.ac.be.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2020 Jan 15; Vol. 500, pp. 110635. Date of Electronic Publication: 2019 Oct 31.
DOI: 10.1016/j.mce.2019.110635
Abstrakt: Thyroid hormone (TH) synthesis requires extracellular hydrogen peroxide generated by the NADPH oxidases, DUOX1 and DUOX2, with maturation factors, DUOXA1 and DUOXA2. In zebrafish, only one duox and one duoxa gene are present. Using a thyroid-specific reporter line, we investigated the role of Duox and Duoxa for TH biosynthesis in zebrafish larvae. Analysis of several zebrafish duox and duoxa mutant models consistently recovered hypothyroid phenotypes with hyperplastic goiter caused by impaired TH synthesis. Mutant larvae developed enlarged thyroids and showed increased expression of the EGFP reporter and thyroid functional markers including wild-type and mutated duox and duoxa transcripts. Treatment of zebrafish larvae with the NADPH oxidase inhibitor VAS2870 phenocopied the thyroid effects observed in duox or duoxa mutants. Additional functional in vitro assays corroborated the pharmacological inhibition of Duox activity by VAS2870. These data support the utility of this new experimental model to characterize endocrine disruptors of the thyroid function.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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