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
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/84201
Ver los metadatos del registro completo
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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 |
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article |
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http://sedici.unlp.edu.ar/handle/10915/84201 |
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eng |
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eng |
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http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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