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dc.contributor.author Nolly, Mariela Beatriz
dc.contributor.author Caldiz, Claudia Irma
dc.contributor.author Yeves, Alejandra del Milagro
dc.contributor.author Villa Abrille, M. C.
dc.contributor.author Morgan, Patricio Eduardo
dc.contributor.author Mondaca, Nicolás Amado
dc.contributor.author Portiansky, Enrique Leo
dc.contributor.author Chiappe, Gladys Ethel
dc.contributor.author Cingolani, Horacio Eugenio
dc.contributor.author Ennis, Irene Lucia
dc.date.available 2017-01-26T20:10:14Z
dc.date.issued 2014-02
dc.identifier.citation Nolly, Mariela Beatriz; Caldiz, Claudia Irma; Yeves, Alejandra del Milagro; Villa Abrille, M. C.; Morgan, Patricio Eduardo; et al.; The signaling pathway for aldosterone-induced mitochondrial production of superoxide anion in the myocardium; elsevire; Journal Of Molecular And Cellular Cardiology; 67; 2-2014; 60-68
dc.identifier.issn 0022-2828
dc.identifier.uri http://hdl.handle.net/11336/12020
dc.description.abstract Mineralocorticoid receptor (MR) antagonists decrease morbidity and mortality in heart failure patients for whom oxidative stress is usual; however, the underlying mechanism for this protection is unclear. Since aldosterone stimulates reactive oxygen species (ROS) production in several tissues, we explored its effect and the intracellular pathway involved in the rat myocardium. Aldosterone dose-dependently increased O2− production in myocardial slices. At 10 nmol/L, aldosterone increased O2− to 165 ± 8.8% of control, an effect prevented not only by the MR antagonists eplerenone and spironolactone (107 ± 7.8 and 103 ± 5.3%, respectively) but also by AG1478 (105 ± 8.0%), antagonist of the EGF receptor (EGFR). Similar results were obtained by silencing MR expression through the direct intramyocardial injection of a lentivirus coding for a siRNA against the MR. The aldosterone effect on O2− production was mimicked by the mKATP channel opener diazoxide and blocked by preventing its opening with 5-HD and glibenclamide, implicating the mitochondria as the source of O2−. Inhibiting the respiratory chain with rotenone or mitochondrial permeability transition (MPT) with cyclosporine A or bongkrekic acid also canceled aldosterone-induced O2− production. In addition, aldosterone effect depended on NADPH oxidase and phosphoinositide 3-kinase activation, as apocynin and wortmannin, respectively, inhibited it. EGF (0.1 μg/mL) similarly increased O2−, although in this case MR antagonists had no effect, suggesting that EGFR transactivation occurred downstream from MR activation. Inhibition of mKATP channels, the respiratory chain, or MPT did not prevent Akt phosphorylation, supporting that it happened upstream of the mitochondria. Importantly, cardiomyocytes were confirmed as a source of aldosterone induced mitochondrial ROS production in experiments performed in isolated cardiac myocytes. These results allow us to speculate that the beneficial effects of MR antagonists in heart failure may be related to a decrease in oxidative stress.
dc.format application/pdf
dc.language.iso eng
dc.publisher elsevire
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject Mineralocorticoid receptor
dc.subject Oxidative stress
dc.subject siRNA
dc.subject Transactivation
dc.subject.classification Fisiología
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title The signaling pathway for aldosterone-induced mitochondrial production of superoxide anion in the myocardium
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-01-25T13:58:22Z
dc.journal.volume 67
dc.journal.pagination 60-68
dc.journal.pais Países Bajos
dc.journal.ciudad Amsterdam
dc.description.fil Fil: Nolly, Mariela Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil Fil: Caldiz, Claudia Irma. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil Fil: Yeves, Alejandra del Milagro. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil Fil: Villa Abrille, M. C.. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil Fil: Morgan, Patricio Eduardo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil Fil: Mondaca, Nicolás Amado. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil Fil: Portiansky, Enrique Leo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil Fil: Chiappe, Gladys Ethel. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil Fil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil Fil: Ennis, Irene Lucia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.journal.title Journal Of Molecular And Cellular Cardiology
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.yjmcc.2013.12.004
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0022282813003532


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