Mostrar el registro sencillo del ítem
dc.contributor.author
Ziros, Panos G
dc.contributor.author
Habeos, Ioannis
dc.contributor.author
Chartoumpekis, Dionysios V
dc.contributor.author
Ntalampyra, Eleni
dc.contributor.author
Somm, Emmanuel
dc.contributor.author
Renaud, Cédric O.
dc.contributor.author
Bongiovanni, Massimo
dc.contributor.author
Trougakos, Ioannis P
dc.contributor.author
Yamamoto, Masayuki
dc.contributor.author
Kensler, Thomas W.
dc.contributor.author
Santisteban, Pilar
dc.contributor.author
Carrasco, Nancy
dc.contributor.author
Ris Stalpers, Carrie
dc.contributor.author
Amendola, Elena
dc.contributor.author
Liao, Xiao-Hui
dc.contributor.author
Rossich, Luciano Esteban
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Thomasz, Lisa
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Juvenal, Guillermo Juan
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Refetoff, Samuel
dc.contributor.author
Sykiotis, Gerasimos P.
dc.date.available
2020-02-05T19:55:36Z
dc.date.issued
2018-06
dc.identifier.citation
Ziros, Panos G; Habeos, Ioannis; Chartoumpekis, Dionysios V; Ntalampyra, Eleni; Somm, Emmanuel; et al.; NFE2-Related transcription factor 2 coordinates antioxidant defense with thyroglobulin production and iodination in the thyroid gland; Mary Ann Liebert; Thyroid; 28; 6; 6-2018; 780-798
dc.identifier.issn
1050-7256
dc.identifier.uri
http://hdl.handle.net/11336/96778
dc.description.abstract
Background: The thyroid gland has a special relationship with oxidative stress. While generation of oxidative substances is part of normal iodide metabolism during thyroid hormone synthesis, the gland must also defend itself against excessive oxidation in order to maintain normal function. Antioxidant and detoxification enzymes aid thyroid cells to maintain homeostasis by ameliorating oxidative insults, including during exposure to excess iodide, but the factors that coordinate their expression with the cellular redox status are not known. The antioxidant response system comprising the ubiquitously expressed NFE2-related transcription factor 2 (Nrf2) and its redox-sensitive cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) defends tissues against oxidative stress, thereby protecting against pathologies that relate to DNA, protein, and/or lipid oxidative damage. Thus, it was hypothesized that Nrf2 should also have important roles in maintaining thyroid homeostasis. Methods: Ubiquitous and thyroid-specific male C57BL6J Nrf2 knockout (Nrf2-KO) mice were studied. Plasma and thyroids were harvested for evaluation of thyroid function tests by radioimmunoassays and of gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Nrf2-KO and Keap1-KO clones of the PCCL3 rat thyroid follicular cell line were generated using CRISPR/Cas9 technology and were used for gene and protein expression studies. Software-predicted Nrf2 binding sites on the thyroglobulin enhancer were validated by site-directed in vitro mutagenesis and chromatin immunoprecipitation. Results: The study shows that Nrf2 mediates antioxidant transcriptional responses in thyroid cells and protects the thyroid from oxidation induced by iodide overload. Surprisingly, it was also found that Nrf2 has a dramatic impact on both the basal abundance and the thyrotropin-inducible intrathyroidal abundance of thyroglobulin (Tg), the precursor protein of thyroid hormones. This effect is mediated by cell-autonomous regulation of Tg gene expression by Nrf2 via its direct binding to two evolutionarily conserved antioxidant response elements in an upstream enhancer. Yet, despite upregulating Tg levels, Nrf2 limits Tg iodination both under basal conditions and in response to excess iodide. Conclusions: Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Mary Ann Liebert
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ANIMAL TESTING ALTERNATIVES
dc.subject
IODIDE
dc.subject
NRF2
dc.subject
OXIDATIVE STRESS
dc.subject
THYROGLOBULIN
dc.subject
THYROID
dc.subject.classification
Bioquímica y Biología Molecular
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Medicina Básica
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
NFE2-Related transcription factor 2 coordinates antioxidant defense with thyroglobulin production and iodination in the thyroid gland
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-12-20T22:57:20Z
dc.journal.volume
28
dc.journal.number
6
dc.journal.pagination
780-798
dc.journal.pais
Estados Unidos
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Ziros, Panos G. Lausanne University; Suiza
dc.description.fil
Fil: Habeos, Ioannis. Patras University; Grecia
dc.description.fil
Fil: Chartoumpekis, Dionysios V. University of Pittsburgh; Estados Unidos
dc.description.fil
Fil: Ntalampyra, Eleni. Universite de Lausanne; Suiza
dc.description.fil
Fil: Somm, Emmanuel. Universite de Lausanne; Suiza
dc.description.fil
Fil: Renaud, Cédric O.. Universite de Lausanne; Suiza
dc.description.fil
Fil: Bongiovanni, Massimo. Institute Of Pathology Locarno; Suiza
dc.description.fil
Fil: Trougakos, Ioannis P. Universidad Nacional y Kapodistríaca de Atenas; Grecia
dc.description.fil
Fil: Yamamoto, Masayuki. University Of Tohoku; Japón
dc.description.fil
Fil: Kensler, Thomas W.. University of Pittsburgh at Johnstown; Estados Unidos
dc.description.fil
Fil: Santisteban, Pilar. Universidad Autónoma de Madrid; España
dc.description.fil
Fil: Carrasco, Nancy. University of Yale. School of Medicine; Estados Unidos
dc.description.fil
Fil: Ris Stalpers, Carrie. Academic Medical Center; Países Bajos
dc.description.fil
Fil: Amendola, Elena. Universidad de Nápoles; Italia
dc.description.fil
Fil: Liao, Xiao-Hui. University of Chicago; Estados Unidos
dc.description.fil
Fil: Rossich, Luciano Esteban. Comisión Nacional de Energía Atómica de Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Thomasz, Lisa. Comisión Nacional de Energía Atómica de Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Juvenal, Guillermo Juan. Comisión Nacional de Energía Atómica de Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Refetoff, Samuel. University of Chicago; Estados Unidos
dc.description.fil
Fil: Sykiotis, Gerasimos P.. Universite de Lausanne; Suiza
dc.journal.title
Thyroid
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.liebertpub.com/doi/10.1089/thy.2018.0018
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1089/thy.2018.0018
Archivos asociados