Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels

Autores
Montesinos, Maria del Mar; Nicola, Juan Pablo; Nazar, Magalí; Peyret, Victoria; Lucero, Ariel Maximiliano; Pellizas, Claudia Gabriela; Masini, Ana María
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Thyroid peroxidase (TPO) is essential for thyroid hormone synthesis mediating the covalent incorporation of iodine into tyrosine residues of thyroglobulin process known as organification. Thyroid-stimulating hormone (TSH) via cAMP signaling is the main hormonal regulator of TPO gene expression. In thyroid cells, TSH-stimulated nitric oxide (NO) production inhibits TSH-induced thyroid-specific gene expression, suggesting a potential autocrine role of NO in modulating thyroid function. Indeed, NO donors downregulate TSH-induced iodide accumulation and organification in thyroid cells. Here, using FRTL-5 thyroid cells as model, we obtained insights into the molecular mechanism underlying the inhibitory effects of NO on iodide organification. We demonstrated that NO donors inhibited TSH-stimulated TPO expression by inducing a cyclic guanosine monophosphate-dependent protein kinase-mediated transcriptional repression of the TPO gene. Moreover, we characterized the FoxE1 binding site Z as mediator of the NO-inhibited TPO expression. Mechanistically, we demonstrated that NO decreases TSH-induced FoxE1 expression, thus repressing the transcripcional activation of TPO gene. Taken together, we provide novel evidence reinforcing the inhibitory role of NO on thyroid cell function, an observation of potential pathophysiological relevance associated with human thyroid pathologies that come along with changes in the NO production.
Fil: Montesinos, Maria del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Nazar, Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Peyret, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Lucero, Ariel Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Masini, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
FORKHEAD BOX PROTEIN E1 (FOXE1)
NITRIC OXIDE (NO)
THYROID STIMULATING HORMONE (TSH)
THYROPEROXIDASE (TPO)
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/185964
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/185964
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levelsMontesinos, Maria del MarNicola, Juan PabloNazar, MagalíPeyret, VictoriaLucero, Ariel MaximilianoPellizas, Claudia GabrielaMasini, Ana MaríaFORKHEAD BOX PROTEIN E1 (FOXE1)NITRIC OXIDE (NO)THYROID STIMULATING HORMONE (TSH)THYROPEROXIDASE (TPO)https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Thyroid peroxidase (TPO) is essential for thyroid hormone synthesis mediating the covalent incorporation of iodine into tyrosine residues of thyroglobulin process known as organification. Thyroid-stimulating hormone (TSH) via cAMP signaling is the main hormonal regulator of TPO gene expression. In thyroid cells, TSH-stimulated nitric oxide (NO) production inhibits TSH-induced thyroid-specific gene expression, suggesting a potential autocrine role of NO in modulating thyroid function. Indeed, NO donors downregulate TSH-induced iodide accumulation and organification in thyroid cells. Here, using FRTL-5 thyroid cells as model, we obtained insights into the molecular mechanism underlying the inhibitory effects of NO on iodide organification. We demonstrated that NO donors inhibited TSH-stimulated TPO expression by inducing a cyclic guanosine monophosphate-dependent protein kinase-mediated transcriptional repression of the TPO gene. Moreover, we characterized the FoxE1 binding site Z as mediator of the NO-inhibited TPO expression. Mechanistically, we demonstrated that NO decreases TSH-induced FoxE1 expression, thus repressing the transcripcional activation of TPO gene. Taken together, we provide novel evidence reinforcing the inhibitory role of NO on thyroid cell function, an observation of potential pathophysiological relevance associated with human thyroid pathologies that come along with changes in the NO production.Fil: Montesinos, Maria del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Nazar, Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Peyret, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Lucero, Ariel Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Masini, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaElsevier Ireland2016-01-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/185964Montesinos, Maria del Mar; Nicola, Juan Pablo; Nazar, Magalí; Peyret, Victoria; Lucero, Ariel Maximiliano; et al.; Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels; Elsevier Ireland; Molecular and Cellular Endocrinology; 420; 15-1-2016; 105-1150303-7207CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2015.11.020info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0303720715301453info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:32:38Zoai:ri.conicet.gov.ar:11336/185964instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:32:38.571CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels
title Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels
spellingShingle Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels
Montesinos, Maria del Mar
FORKHEAD BOX PROTEIN E1 (FOXE1)
NITRIC OXIDE (NO)
THYROID STIMULATING HORMONE (TSH)
THYROPEROXIDASE (TPO)
title_short Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels
title_full Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels
title_fullStr Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels
title_full_unstemmed Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels
title_sort Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels
dc.creator.none.fl_str_mv Montesinos, Maria del Mar
Nicola, Juan Pablo
Nazar, Magalí
Peyret, Victoria
Lucero, Ariel Maximiliano
Pellizas, Claudia Gabriela
Masini, Ana María
author Montesinos, Maria del Mar
author_facet Montesinos, Maria del Mar
Nicola, Juan Pablo
Nazar, Magalí
Peyret, Victoria
Lucero, Ariel Maximiliano
Pellizas, Claudia Gabriela
Masini, Ana María
author_role author
author2 Nicola, Juan Pablo
Nazar, Magalí
Peyret, Victoria
Lucero, Ariel Maximiliano
Pellizas, Claudia Gabriela
Masini, Ana María
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv FORKHEAD BOX PROTEIN E1 (FOXE1)
NITRIC OXIDE (NO)
THYROID STIMULATING HORMONE (TSH)
THYROPEROXIDASE (TPO)
topic FORKHEAD BOX PROTEIN E1 (FOXE1)
NITRIC OXIDE (NO)
THYROID STIMULATING HORMONE (TSH)
THYROPEROXIDASE (TPO)
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Thyroid peroxidase (TPO) is essential for thyroid hormone synthesis mediating the covalent incorporation of iodine into tyrosine residues of thyroglobulin process known as organification. Thyroid-stimulating hormone (TSH) via cAMP signaling is the main hormonal regulator of TPO gene expression. In thyroid cells, TSH-stimulated nitric oxide (NO) production inhibits TSH-induced thyroid-specific gene expression, suggesting a potential autocrine role of NO in modulating thyroid function. Indeed, NO donors downregulate TSH-induced iodide accumulation and organification in thyroid cells. Here, using FRTL-5 thyroid cells as model, we obtained insights into the molecular mechanism underlying the inhibitory effects of NO on iodide organification. We demonstrated that NO donors inhibited TSH-stimulated TPO expression by inducing a cyclic guanosine monophosphate-dependent protein kinase-mediated transcriptional repression of the TPO gene. Moreover, we characterized the FoxE1 binding site Z as mediator of the NO-inhibited TPO expression. Mechanistically, we demonstrated that NO decreases TSH-induced FoxE1 expression, thus repressing the transcripcional activation of TPO gene. Taken together, we provide novel evidence reinforcing the inhibitory role of NO on thyroid cell function, an observation of potential pathophysiological relevance associated with human thyroid pathologies that come along with changes in the NO production.
Fil: Montesinos, Maria del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Nazar, Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Peyret, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Lucero, Ariel Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Masini, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Thyroid peroxidase (TPO) is essential for thyroid hormone synthesis mediating the covalent incorporation of iodine into tyrosine residues of thyroglobulin process known as organification. Thyroid-stimulating hormone (TSH) via cAMP signaling is the main hormonal regulator of TPO gene expression. In thyroid cells, TSH-stimulated nitric oxide (NO) production inhibits TSH-induced thyroid-specific gene expression, suggesting a potential autocrine role of NO in modulating thyroid function. Indeed, NO donors downregulate TSH-induced iodide accumulation and organification in thyroid cells. Here, using FRTL-5 thyroid cells as model, we obtained insights into the molecular mechanism underlying the inhibitory effects of NO on iodide organification. We demonstrated that NO donors inhibited TSH-stimulated TPO expression by inducing a cyclic guanosine monophosphate-dependent protein kinase-mediated transcriptional repression of the TPO gene. Moreover, we characterized the FoxE1 binding site Z as mediator of the NO-inhibited TPO expression. Mechanistically, we demonstrated that NO decreases TSH-induced FoxE1 expression, thus repressing the transcripcional activation of TPO gene. Taken together, we provide novel evidence reinforcing the inhibitory role of NO on thyroid cell function, an observation of potential pathophysiological relevance associated with human thyroid pathologies that come along with changes in the NO production.
publishDate 2016
dc.date.none.fl_str_mv 2016-01-15
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/185964
Montesinos, Maria del Mar; Nicola, Juan Pablo; Nazar, Magalí; Peyret, Victoria; Lucero, Ariel Maximiliano; et al.; Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels; Elsevier Ireland; Molecular and Cellular Endocrinology; 420; 15-1-2016; 105-115
0303-7207
CONICET Digital
CONICET
url http://hdl.handle.net/11336/185964
identifier_str_mv Montesinos, Maria del Mar; Nicola, Juan Pablo; Nazar, Magalí; Peyret, Victoria; Lucero, Ariel Maximiliano; et al.; Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels; Elsevier Ireland; Molecular and Cellular Endocrinology; 420; 15-1-2016; 105-115
0303-7207
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2015.11.020
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0303720715301453
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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