Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor

Autores
De Giusti, Verónica Celeste; Nolly, Mariela; Yeves, Alejandra M.; Caldiz, Claudia Irma; Villa Abrille, María Celeste; Chiappe de Cingolani, Gladys Ethel; Ennis, Irene Lucía; Cingolani, Horacio Eugenio; Aiello, Ernesto Alejandro
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The use of antagonists of the mineralocorticoid receptor in the treatment of myocardial hypertrophy and heart failure has gained increasing importance in the last years. The cardiac Na/H exchanger (NHE-1) upregulation induced by aldosterone could account for the genesis of these pathologies. We tested whether aldosterone-induced NHE-1 stimulation involves the transactivation of the epidermal growth factor receptor (EGFR). Rat ventricular myocytes were used to measure intracellular pH with epifluorescence. Aldosterone enhanced the NHE-1 activity. This effect was canceled by spironolactone or eplerenone (mineralocorticoid receptor antagonists), but not by mifepristone (glucocorticoid receptor antagonist) or cycloheximide (protein synthesis inhibitor), indicating that the mechanism is mediated by the mineralocorticoid receptor triggering nongenomic pathways. Aldosterone-induced NHE-1 stimulation was abolished by the EGFR kinase inhibitor AG1478, suggesting that is mediated by transactivation of EGFR. The increase in the phosphorylation level of the kinase p90 RSK and NHE-1 serine703 induced by aldosterone was also blocked by AG1478. Exogenous epidermal growth factor mimicked the effects of aldosterone on NHE-1 activity. Epidermal growth factor was also able to increase reactive oxygen species production, and the epidermal growth factor-induced activation of the NHE-1 was abrogated by the reactive oxygen species scavenger N-2-mercaptopropionyl glycine, indicating that reactive oxygen species are participating as signaling molecules in this mechanism. Aldosterone enhances the NHE-1 activity via transactivation of the EGFR, formation of reactive oxygen species, and phosphorylation of the exchanger. These results call attention to the consideration of the EGFR as a new potential therapeutic target of the cardiovascular pathologies involving the participation of aldosterone.
Facultad de Ciencias Médicas
Materia
Ciencias Médicas
Aldosterone
Cardiac myocytes
Epidermal growth factor receptor
Sodium/hydrogen exchanger
Transactivation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/84201

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repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptorDe Giusti, Verónica CelesteNolly, MarielaYeves, Alejandra M.Caldiz, Claudia IrmaVilla Abrille, María CelesteChiappe de Cingolani, Gladys EthelEnnis, Irene LucíaCingolani, Horacio EugenioAiello, Ernesto AlejandroCiencias MédicasAldosteroneCardiac myocytesEpidermal growth factor receptorSodium/hydrogen exchangerTransactivationThe use of antagonists of the mineralocorticoid receptor in the treatment of myocardial hypertrophy and heart failure has gained increasing importance in the last years. The cardiac Na/H exchanger (NHE-1) upregulation induced by aldosterone could account for the genesis of these pathologies. We tested whether aldosterone-induced NHE-1 stimulation involves the transactivation of the epidermal growth factor receptor (EGFR). Rat ventricular myocytes were used to measure intracellular pH with epifluorescence. Aldosterone enhanced the NHE-1 activity. This effect was canceled by spironolactone or eplerenone (mineralocorticoid receptor antagonists), but not by mifepristone (glucocorticoid receptor antagonist) or cycloheximide (protein synthesis inhibitor), indicating that the mechanism is mediated by the mineralocorticoid receptor triggering nongenomic pathways. Aldosterone-induced NHE-1 stimulation was abolished by the EGFR kinase inhibitor AG1478, suggesting that is mediated by transactivation of EGFR. The increase in the phosphorylation level of the kinase p90 RSK and NHE-1 serine703 induced by aldosterone was also blocked by AG1478. Exogenous epidermal growth factor mimicked the effects of aldosterone on NHE-1 activity. Epidermal growth factor was also able to increase reactive oxygen species production, and the epidermal growth factor-induced activation of the NHE-1 was abrogated by the reactive oxygen species scavenger N-2-mercaptopropionyl glycine, indicating that reactive oxygen species are participating as signaling molecules in this mechanism. Aldosterone enhances the NHE-1 activity via transactivation of the EGFR, formation of reactive oxygen species, and phosphorylation of the exchanger. These results call attention to the consideration of the EGFR as a new potential therapeutic target of the cardiovascular pathologies involving the participation of aldosterone.Facultad de Ciencias Médicas2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf912-919http://sedici.unlp.edu.ar/handle/10915/84201enginfo:eu-repo/semantics/altIdentifier/issn/0194-911Xinfo:eu-repo/semantics/altIdentifier/doi/10.1161/HYPERTENSIONAHA.111.176024info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:16:06Zoai:sedici.unlp.edu.ar:10915/84201Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:16:06.372SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor
title Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor
spellingShingle Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor
De Giusti, Verónica Celeste
Ciencias Médicas
Aldosterone
Cardiac myocytes
Epidermal growth factor receptor
Sodium/hydrogen exchanger
Transactivation
title_short Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor
title_full Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor
title_fullStr Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor
title_full_unstemmed Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor
title_sort Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor
dc.creator.none.fl_str_mv De Giusti, Verónica Celeste
Nolly, Mariela
Yeves, Alejandra M.
Caldiz, Claudia Irma
Villa Abrille, María Celeste
Chiappe de Cingolani, Gladys Ethel
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
Aiello, Ernesto Alejandro
author De Giusti, Verónica Celeste
author_facet De Giusti, Verónica Celeste
Nolly, Mariela
Yeves, Alejandra M.
Caldiz, Claudia Irma
Villa Abrille, María Celeste
Chiappe de Cingolani, Gladys Ethel
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
Aiello, Ernesto Alejandro
author_role author
author2 Nolly, Mariela
Yeves, Alejandra M.
Caldiz, Claudia Irma
Villa Abrille, María Celeste
Chiappe de Cingolani, Gladys Ethel
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
Aiello, Ernesto Alejandro
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Aldosterone
Cardiac myocytes
Epidermal growth factor receptor
Sodium/hydrogen exchanger
Transactivation
topic Ciencias Médicas
Aldosterone
Cardiac myocytes
Epidermal growth factor receptor
Sodium/hydrogen exchanger
Transactivation
dc.description.none.fl_txt_mv The use of antagonists of the mineralocorticoid receptor in the treatment of myocardial hypertrophy and heart failure has gained increasing importance in the last years. The cardiac Na/H exchanger (NHE-1) upregulation induced by aldosterone could account for the genesis of these pathologies. We tested whether aldosterone-induced NHE-1 stimulation involves the transactivation of the epidermal growth factor receptor (EGFR). Rat ventricular myocytes were used to measure intracellular pH with epifluorescence. Aldosterone enhanced the NHE-1 activity. This effect was canceled by spironolactone or eplerenone (mineralocorticoid receptor antagonists), but not by mifepristone (glucocorticoid receptor antagonist) or cycloheximide (protein synthesis inhibitor), indicating that the mechanism is mediated by the mineralocorticoid receptor triggering nongenomic pathways. Aldosterone-induced NHE-1 stimulation was abolished by the EGFR kinase inhibitor AG1478, suggesting that is mediated by transactivation of EGFR. The increase in the phosphorylation level of the kinase p90 RSK and NHE-1 serine703 induced by aldosterone was also blocked by AG1478. Exogenous epidermal growth factor mimicked the effects of aldosterone on NHE-1 activity. Epidermal growth factor was also able to increase reactive oxygen species production, and the epidermal growth factor-induced activation of the NHE-1 was abrogated by the reactive oxygen species scavenger N-2-mercaptopropionyl glycine, indicating that reactive oxygen species are participating as signaling molecules in this mechanism. Aldosterone enhances the NHE-1 activity via transactivation of the EGFR, formation of reactive oxygen species, and phosphorylation of the exchanger. These results call attention to the consideration of the EGFR as a new potential therapeutic target of the cardiovascular pathologies involving the participation of aldosterone.
Facultad de Ciencias Médicas
description The use of antagonists of the mineralocorticoid receptor in the treatment of myocardial hypertrophy and heart failure has gained increasing importance in the last years. The cardiac Na/H exchanger (NHE-1) upregulation induced by aldosterone could account for the genesis of these pathologies. We tested whether aldosterone-induced NHE-1 stimulation involves the transactivation of the epidermal growth factor receptor (EGFR). Rat ventricular myocytes were used to measure intracellular pH with epifluorescence. Aldosterone enhanced the NHE-1 activity. This effect was canceled by spironolactone or eplerenone (mineralocorticoid receptor antagonists), but not by mifepristone (glucocorticoid receptor antagonist) or cycloheximide (protein synthesis inhibitor), indicating that the mechanism is mediated by the mineralocorticoid receptor triggering nongenomic pathways. Aldosterone-induced NHE-1 stimulation was abolished by the EGFR kinase inhibitor AG1478, suggesting that is mediated by transactivation of EGFR. The increase in the phosphorylation level of the kinase p90 RSK and NHE-1 serine703 induced by aldosterone was also blocked by AG1478. Exogenous epidermal growth factor mimicked the effects of aldosterone on NHE-1 activity. Epidermal growth factor was also able to increase reactive oxygen species production, and the epidermal growth factor-induced activation of the NHE-1 was abrogated by the reactive oxygen species scavenger N-2-mercaptopropionyl glycine, indicating that reactive oxygen species are participating as signaling molecules in this mechanism. Aldosterone enhances the NHE-1 activity via transactivation of the EGFR, formation of reactive oxygen species, and phosphorylation of the exchanger. These results call attention to the consideration of the EGFR as a new potential therapeutic target of the cardiovascular pathologies involving the participation of aldosterone.
publishDate 2011
dc.date.none.fl_str_mv 2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/84201
url http://sedici.unlp.edu.ar/handle/10915/84201
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0194-911X
info:eu-repo/semantics/altIdentifier/doi/10.1161/HYPERTENSIONAHA.111.176024
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
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