Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor
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 test...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
2011
|
| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/84201 |
| Aporte de: |
| id |
I19-R120-10915-84201 |
|---|---|
| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Médicas Aldosterone Cardiac myocytes Epidermal growth factor receptor Sodium/hydrogen exchanger Transactivation |
| spellingShingle |
Ciencias Médicas Aldosterone Cardiac myocytes Epidermal growth factor receptor Sodium/hydrogen exchanger Transactivation 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 Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor |
| topic_facet |
Ciencias Médicas Aldosterone Cardiac myocytes Epidermal growth factor receptor Sodium/hydrogen exchanger Transactivation |
| 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. |
| format |
Articulo Articulo |
| author |
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_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_sort |
De Giusti, Verónica Celeste |
| title |
Aldosterone stimulates the cardiac Na +/H + exchanger via transactivation of the epidermal growth factor receptor |
| 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 |
| publishDate |
2011 |
| url |
http://sedici.unlp.edu.ar/handle/10915/84201 |
| work_keys_str_mv |
AT degiustiveronicaceleste aldosteronestimulatesthecardiacnahexchangerviatransactivationoftheepidermalgrowthfactorreceptor AT nollymariela aldosteronestimulatesthecardiacnahexchangerviatransactivationoftheepidermalgrowthfactorreceptor AT yevesalejandram aldosteronestimulatesthecardiacnahexchangerviatransactivationoftheepidermalgrowthfactorreceptor AT caldizclaudiairma aldosteronestimulatesthecardiacnahexchangerviatransactivationoftheepidermalgrowthfactorreceptor AT villaabrillemariaceleste aldosteronestimulatesthecardiacnahexchangerviatransactivationoftheepidermalgrowthfactorreceptor AT chiappedecingolanigladysethel aldosteronestimulatesthecardiacnahexchangerviatransactivationoftheepidermalgrowthfactorreceptor AT ennisirenelucia aldosteronestimulatesthecardiacnahexchangerviatransactivationoftheepidermalgrowthfactorreceptor AT cingolanihoracioeugenio aldosteronestimulatesthecardiacnahexchangerviatransactivationoftheepidermalgrowthfactorreceptor AT aielloernestoalejandro aldosteronestimulatesthecardiacnahexchangerviatransactivationoftheepidermalgrowthfactorreceptor |
| bdutipo_str |
Repositorios |
| _version_ |
1764820488467513346 |