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dc.contributor.author
Villa-Abrille, María Celeste
dc.contributor.author
Cingolani, Horacio Eugenio
dc.contributor.author
Cingolani, Horacio Eugenio
dc.contributor.author
Alvarez, Bernardo
dc.date.available
2018-10-10T20:21:30Z
dc.date.issued
2011-04
dc.identifier.citation
Villa-Abrille, María Celeste; Cingolani, Horacio Eugenio; Cingolani, Horacio Eugenio; Alvarez, Bernardo; Silencing of cardiac mitochondrial NHE1 prevents mitochondrial permeability transition pore opening; American Physiological Society; American Journal of Physiology - Heart and Circulatory Physiology; 300; 4; 4-2011; 1-17
dc.identifier.issn
0363-6135
dc.identifier.uri
http://hdl.handle.net/11336/62143
dc.description.abstract
Inhibition of Na +/H + exchanger 1 (NHE1) reduces cardiac ischemia-reperfusion (I/R) injury and also cardiac hypertrophy and failure. Although the mechanisms underlying these NHE1-mediated effects suggest delay of mitochondrial permeability transition pore (MPTP) opening, and reduction of mitochon-drial-derived superoxide production, the possibility of NHE1 blockade targeting mitochondria has been incompletely explored. A short-hairpin RNA sequence mediating specific knock down of NHE1 expression was incorporated into a lentiviral vector (shRNA-NHE1) and transduced in the rat myocardium. NHE1 expression of mitochondrial lysates revealed that shRNA-NHE1 transductions reduced mitochondrial NHE1 (mNHE1) by ~60%, supporting the expression of NHE1 in mitochondria membranes. Electron microscopy studies corroborate the presence of NHE1 in heart mitochondria. Immunostain-ing of rat cardiomyocytes also suggests colocalization of NHE1 with the mitochondrial marker cytochrome c oxidase. To examine the functional role of mNHE1, mitochondrial suspensions were exposed to increasing concentrations of CaCl 2 to induce MPTP opening and consequently mitochondrial swelling. shRNA-NHE1 transduction reduced CaCl 2-induced mitochondrial swelling by 64 ± 4%. Whereas the NHE1 inhibitor HOE-642 (10 (xM) decreased mitochondrial Ca 2+-induced swelling in rats transduced with nonsilencing RNAi (37 ± 6%), no additional HOE-642 effects were detected in mitochondria from rats transduced with shRNA-NHE1. We have characterized the expression and function of NHE1 in rat heart mitochondria. Because mitochondria from rats injected with shRNA-NHE1 present a high threshold for MPTP formation, the beneficial effects of NHE1 inhibition in I/R resulting from mitochondrial targeting should be considered. © 2011 the American Physiological Society.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Physiological Society
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Ischemia
dc.subject
Mitochondrial Permeability Transition Pore
dc.subject
Myocardium
dc.subject.classification
Inmunología
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Silencing of cardiac mitochondrial NHE1 prevents mitochondrial permeability transition pore opening
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-09-10T16:43:38Z
dc.journal.volume
300
dc.journal.number
4
dc.journal.pagination
1-17
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Villa-Abrille, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
dc.description.fil
Fil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Heart Institute Cedars; Estados Unidos
dc.description.fil
Fil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
dc.description.fil
Fil: Alvarez, Bernardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
dc.journal.title
American Journal of Physiology - Heart and Circulatory Physiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1152/ajpheart.00840.2010
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/ajpheart.00840.2010


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