The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway

Autores
Serrano Nascimento, Caroline; da Silva Teixeira, Silvania; Nicola, Juan Pablo; Nachbar, Renato Tadeu; Masini, Ana María; Nunes, Maria Tereza
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Iodide (I−) is an irreplaceable constituent of thyroid hormones and an important regulator of thyroid function, because high concentrations of I− down-regulate sodium/iodide symporter (NIS) expression and function. In thyrocytes, activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) cascade also inhibits NIS expression and function. Because I− excess and PI3K/Akt signaling pathway induce similar inhibitory effects on NIS expression, we aimed to study whether the PI3K/Akt cascade mediates the acute and rapid inhibitory effect of I− excess on NIS expression/activity. Here, we reported that the treatment of PCCl3 cells with I− excess increased Akt phosphorylation under normal or TSH/insulin-starving conditions. I− stimulated Akt phosphorylation in a PI3K-dependent manner, because the use of PI3K inhibitors (wortmannin or 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) abrogated the induction of I− effect. Moreover, I− inhibitory effect on NIS expression and function were abolished when the cells were previously treated with specific inhibitors of PI3K or Akt (Akt1/2 kinase inhibitor). Importantly, we also found that the effect of I− on NIS expression involved the generation of reactive oxygen species (ROS). Using the fluorogenic probes dihydroethidium and mitochondrial superoxide indicator (MitoSOX Red), we observed that I− excess increased ROS production in thyrocytes and determined that mitochondria were the source of anion superoxide. Furthermore, the ROS scavengers N-acetyl cysteine and 2-phenyl-1,2-benzisoselenazol-3-(2H)-one blocked the effect of I− on Akt phosphorylation. Overall, our data demonstrated the involvement of the PI3K/Akt signaling pathway as a novel mediator of the I−-induced thyroid autoregulation, linking the role of thyroid oxidative state to the Wolff-Chaikoff effect.
Fil: Serrano Nascimento, Caroline. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil
Fil: da Silva Teixeira, Silvania. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil
Fil: Nicola, Juan Pablo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nachbar, Renato Tadeu. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil
Fil: Masini, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nunes, Maria Tereza. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil
Materia
Sodium-Iodide Symporter (Nis)
Pi3k/Akt Cascade
Reactive Oxygen Species (Ros)
Thyroid Autoregulation
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:11336/31871
Acceder
id CONICETDig_b5bbd7dfc611cef2fbbaf30f34dea157
oai_identifier_str oai:ri.conicet.gov.ar:11336/31871
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling PathwaySerrano Nascimento, Carolineda Silva Teixeira, SilvaniaNicola, Juan PabloNachbar, Renato TadeuMasini, Ana MaríaNunes, Maria TerezaSodium-Iodide Symporter (Nis)Pi3k/Akt CascadeReactive Oxygen Species (Ros)Thyroid Autoregulationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Iodide (I−) is an irreplaceable constituent of thyroid hormones and an important regulator of thyroid function, because high concentrations of I− down-regulate sodium/iodide symporter (NIS) expression and function. In thyrocytes, activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) cascade also inhibits NIS expression and function. Because I− excess and PI3K/Akt signaling pathway induce similar inhibitory effects on NIS expression, we aimed to study whether the PI3K/Akt cascade mediates the acute and rapid inhibitory effect of I− excess on NIS expression/activity. Here, we reported that the treatment of PCCl3 cells with I− excess increased Akt phosphorylation under normal or TSH/insulin-starving conditions. I− stimulated Akt phosphorylation in a PI3K-dependent manner, because the use of PI3K inhibitors (wortmannin or 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) abrogated the induction of I− effect. Moreover, I− inhibitory effect on NIS expression and function were abolished when the cells were previously treated with specific inhibitors of PI3K or Akt (Akt1/2 kinase inhibitor). Importantly, we also found that the effect of I− on NIS expression involved the generation of reactive oxygen species (ROS). Using the fluorogenic probes dihydroethidium and mitochondrial superoxide indicator (MitoSOX Red), we observed that I− excess increased ROS production in thyrocytes and determined that mitochondria were the source of anion superoxide. Furthermore, the ROS scavengers N-acetyl cysteine and 2-phenyl-1,2-benzisoselenazol-3-(2H)-one blocked the effect of I− on Akt phosphorylation. Overall, our data demonstrated the involvement of the PI3K/Akt signaling pathway as a novel mediator of the I−-induced thyroid autoregulation, linking the role of thyroid oxidative state to the Wolff-Chaikoff effect.Fil: Serrano Nascimento, Caroline. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; BrasilFil: da Silva Teixeira, Silvania. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; BrasilFil: Nicola, Juan Pablo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nachbar, Renato Tadeu. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; BrasilFil: Masini, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nunes, Maria Tereza. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; BrasilEndocrine Society2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/31871Serrano Nascimento, Caroline; da Silva Teixeira, Silvania; Nicola, Juan Pablo; Nachbar, Renato Tadeu; Masini, Ana María; et al.; The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway; Endocrine Society; Endocrinology; 155; 3; 3-2014; 1145-11560013-7227CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article/155/3/1145/2843505info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2013-1665info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:36:18Zoai:ri.conicet.gov.ar:11336/31871instacron: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:34982025-10-15 14:36:18.984CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway
title The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway
spellingShingle The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway
Serrano Nascimento, Caroline
Sodium-Iodide Symporter (Nis)
Pi3k/Akt Cascade
Reactive Oxygen Species (Ros)
Thyroid Autoregulation
title_short The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway
title_full The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway
title_fullStr The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway
title_full_unstemmed The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway
title_sort The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway
dc.creator.none.fl_str_mv Serrano Nascimento, Caroline
da Silva Teixeira, Silvania
Nicola, Juan Pablo
Nachbar, Renato Tadeu
Masini, Ana María
Nunes, Maria Tereza
author Serrano Nascimento, Caroline
author_facet Serrano Nascimento, Caroline
da Silva Teixeira, Silvania
Nicola, Juan Pablo
Nachbar, Renato Tadeu
Masini, Ana María
Nunes, Maria Tereza
author_role author
author2 da Silva Teixeira, Silvania
Nicola, Juan Pablo
Nachbar, Renato Tadeu
Masini, Ana María
Nunes, Maria Tereza
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Sodium-Iodide Symporter (Nis)
Pi3k/Akt Cascade
Reactive Oxygen Species (Ros)
Thyroid Autoregulation
topic Sodium-Iodide Symporter (Nis)
Pi3k/Akt Cascade
Reactive Oxygen Species (Ros)
Thyroid Autoregulation
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Iodide (I−) is an irreplaceable constituent of thyroid hormones and an important regulator of thyroid function, because high concentrations of I− down-regulate sodium/iodide symporter (NIS) expression and function. In thyrocytes, activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) cascade also inhibits NIS expression and function. Because I− excess and PI3K/Akt signaling pathway induce similar inhibitory effects on NIS expression, we aimed to study whether the PI3K/Akt cascade mediates the acute and rapid inhibitory effect of I− excess on NIS expression/activity. Here, we reported that the treatment of PCCl3 cells with I− excess increased Akt phosphorylation under normal or TSH/insulin-starving conditions. I− stimulated Akt phosphorylation in a PI3K-dependent manner, because the use of PI3K inhibitors (wortmannin or 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) abrogated the induction of I− effect. Moreover, I− inhibitory effect on NIS expression and function were abolished when the cells were previously treated with specific inhibitors of PI3K or Akt (Akt1/2 kinase inhibitor). Importantly, we also found that the effect of I− on NIS expression involved the generation of reactive oxygen species (ROS). Using the fluorogenic probes dihydroethidium and mitochondrial superoxide indicator (MitoSOX Red), we observed that I− excess increased ROS production in thyrocytes and determined that mitochondria were the source of anion superoxide. Furthermore, the ROS scavengers N-acetyl cysteine and 2-phenyl-1,2-benzisoselenazol-3-(2H)-one blocked the effect of I− on Akt phosphorylation. Overall, our data demonstrated the involvement of the PI3K/Akt signaling pathway as a novel mediator of the I−-induced thyroid autoregulation, linking the role of thyroid oxidative state to the Wolff-Chaikoff effect.
Fil: Serrano Nascimento, Caroline. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil
Fil: da Silva Teixeira, Silvania. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil
Fil: Nicola, Juan Pablo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nachbar, Renato Tadeu. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil
Fil: Masini, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nunes, Maria Tereza. Universidade do Sao Paulo. Instituto de Ciencias Biomedicas; Brasil
description Iodide (I−) is an irreplaceable constituent of thyroid hormones and an important regulator of thyroid function, because high concentrations of I− down-regulate sodium/iodide symporter (NIS) expression and function. In thyrocytes, activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) cascade also inhibits NIS expression and function. Because I− excess and PI3K/Akt signaling pathway induce similar inhibitory effects on NIS expression, we aimed to study whether the PI3K/Akt cascade mediates the acute and rapid inhibitory effect of I− excess on NIS expression/activity. Here, we reported that the treatment of PCCl3 cells with I− excess increased Akt phosphorylation under normal or TSH/insulin-starving conditions. I− stimulated Akt phosphorylation in a PI3K-dependent manner, because the use of PI3K inhibitors (wortmannin or 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) abrogated the induction of I− effect. Moreover, I− inhibitory effect on NIS expression and function were abolished when the cells were previously treated with specific inhibitors of PI3K or Akt (Akt1/2 kinase inhibitor). Importantly, we also found that the effect of I− on NIS expression involved the generation of reactive oxygen species (ROS). Using the fluorogenic probes dihydroethidium and mitochondrial superoxide indicator (MitoSOX Red), we observed that I− excess increased ROS production in thyrocytes and determined that mitochondria were the source of anion superoxide. Furthermore, the ROS scavengers N-acetyl cysteine and 2-phenyl-1,2-benzisoselenazol-3-(2H)-one blocked the effect of I− on Akt phosphorylation. Overall, our data demonstrated the involvement of the PI3K/Akt signaling pathway as a novel mediator of the I−-induced thyroid autoregulation, linking the role of thyroid oxidative state to the Wolff-Chaikoff effect.
publishDate 2014
dc.date.none.fl_str_mv 2014-03
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/11336/31871
Serrano Nascimento, Caroline; da Silva Teixeira, Silvania; Nicola, Juan Pablo; Nachbar, Renato Tadeu; Masini, Ana María; et al.; The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway; Endocrine Society; Endocrinology; 155; 3; 3-2014; 1145-1156
0013-7227
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31871
identifier_str_mv Serrano Nascimento, Caroline; da Silva Teixeira, Silvania; Nicola, Juan Pablo; Nachbar, Renato Tadeu; Masini, Ana María; et al.; The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway; Endocrine Society; Endocrinology; 155; 3; 3-2014; 1145-1156
0013-7227
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article/155/3/1145/2843505
info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2013-1665
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
dc.publisher.none.fl_str_mv Endocrine Society
publisher.none.fl_str_mv Endocrine Society
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
_version_ 1846082828753698816
score 13.22299

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