CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Mitochondrial Na+/H+ Exchanger 1. A Possible Target for Cardiac Ischemia/Reperfusion Injury.
ALVAREZ BV; VILLA-ABRILLE, MC; CINGOLANI, HE
Congreso; XX Congress of the International Society for Heart Research; 2010
International Society for Heart Research (World Section) -
Inhibition of Na+/H+ exchanger isoform 1 (NHE1) reduces cardiac ischemia/reperfusion injury. The mechanisms underlying this effect mediated by NHE1 blockade suggests maintenance of mitochondrial membrane potential, delay of mitochondrial permeability transition pore opening, and reduction of mitochondrial-derived superoxide production. We characterized the expression of the NHE1 isoform in mitochondria isolated from adult rat hearts. NHE1 protein was detected in mitochondrial lysates, by immunoblots. A short hairpin RNA template sequence capable of mediating the knockdown of the NHE1 gene was incorporated into a lentiviral vector (LV-shNHE1), and injected into the left ventricular wall of adult rats. Expression of NHE1 was then examined in mitochondrial lysates, by immunoblots. LV-shNHE1 injection reduced the expression of mitochondrial NHE1 by 69 ± 1 % (n=3, P<0.05). Immunostaining of isolated cardiomyocytes combined with confocal immunofluorescence microscopy revealed co-localization of NHE1 with citochrome C oxidase Complex I protein, a marker of mitochondria. Finally, immunoelectron microscopy confirmed the presence of NHE1 in cardiac mitochondria. Localization of immunogold particles suggests association of NHE1 with the mitochondrial inner membrane. We have demonstrated by the first time the expression of NHE1 in heart mitochondria. Thus, inhibition of heart mitochondrial NHE1 could be a therapeutic strategy to protect the heart of the ischemia/reperfusion injury.