Compensatory role of the NBCn1 sodium/bicarbonate cotransporter on Ca<SUP>2+</SUP>-induced mitochondrial swelling in hypertrophic hearts

NBC Na<sup>+</sup>/HCO<sub>3</sub> − cotransporter (NBCn1) and NHE1 Na<sup>+</sup>/H<sup>+</sup> exchanger have been associated with cardiac disorders and recently located in coronary endothelial cells (CEC) and cardiomyocytes mitochondria, respectivel...

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Autores principales: Vargas, Lorena Alejandra, Carrizo Velásquez, Fernanda Elisabeth, Álvarez, Bernardo Víctor
Formato: Articulo
Lenguaje:Inglés
Publicado: 2017
Materias:
Ciencias Médicas
Hypertrophy
Mitochondrial permeability transition pore
Myocardium
NBCn1 Na+/HCO3 - cotransporter
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/102178
https://ri.conicet.gov.ar/11336/54406
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-102178
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
Hypertrophy
Mitochondrial permeability transition pore
Myocardium
NBCn1 Na+/HCO3 - cotransporter
spellingShingle Ciencias Médicas
Hypertrophy
Mitochondrial permeability transition pore
Myocardium
NBCn1 Na+/HCO3 - cotransporter
Vargas, Lorena Alejandra
Carrizo Velásquez, Fernanda Elisabeth
Álvarez, Bernardo Víctor
Compensatory role of the NBCn1 sodium/bicarbonate cotransporter on Ca<SUP>2+</SUP>-induced mitochondrial swelling in hypertrophic hearts
topic_facet Ciencias Médicas
Hypertrophy
Mitochondrial permeability transition pore
Myocardium
NBCn1 Na+/HCO3 - cotransporter
description NBC Na<sup>+</sup>/HCO<sub>3</sub> − cotransporter (NBCn1) and NHE1 Na<sup>+</sup>/H<sup>+</sup> exchanger have been associated with cardiac disorders and recently located in coronary endothelial cells (CEC) and cardiomyocytes mitochondria, respectively. Mitochondrial NHE1 blockade delays permeability transition pore (MPTP) opening and reduces superoxide levels, two critical events exacerbated in cells of diseased hearts. Conversely, activation of NBCn1 prevented apoptosis in CEC subjected to ischemic stress. We characterized the role of the NHE1 and NBCn1 transporters in heart mitochondria from hypertrophic (SHR) and control (Wistar) rats. Expression of NHE1 was analyzed in left ventricular mitochondrial lysates (LVML), by immunoblots. NHE1 expression increased by ~40% in SHR compared to control (P < 0.05, n = 4). To examine NHE1-mediated Na<sup>+</sup>/H<sup>+</sup> exchange activity in cardiac hypertrophy, mitochondria were loaded with BCECF-AM dye and the maximal rate of pHm change measured after the addition of 50 mM NaCl. SHR mitochondria had greater changes in pHm compared to Wistar, 0.10 ± 0.01 vs. 0.06 ± 0.01, respectively (P < 0.05, n = 5). In addition, mitochondrial suspensions from SHR and control myocardium were exposed to 200 μM CaCl2 to induce MPTP opening (light-scattering decrease, LSD) and swelling. Surprisingly, SHR rats showed smaller LSD and a reduction in mitochondrial swelling, 67 ± 10% (n = 15), compared to control, 100 ± 8% (n = 13). NBC inhibition with S0859 (1 μM) significantly increased swelling in both control 139 ± 10% (n = 8) and SHR 115 ± 10% (n = 4). Finally, NBCn1 Na<sup>+</sup>/HCO<sub>3</sub> − cotransporter increased by twofold its expression in SHR LVML, compared to normal (P < 0.05, n = 5). We conclude that increased NBCn1 activity may play a compensatory role in hypertrophic hearts, protecting mitochondria from Ca<sup2+</sup>-induced MPTP opening and swelling.
format Articulo
Articulo
author Vargas, Lorena Alejandra
Carrizo Velásquez, Fernanda Elisabeth
Álvarez, Bernardo Víctor
author_facet Vargas, Lorena Alejandra
Carrizo Velásquez, Fernanda Elisabeth
Álvarez, Bernardo Víctor
author_sort Vargas, Lorena Alejandra
title Compensatory role of the NBCn1 sodium/bicarbonate cotransporter on Ca<SUP>2+</SUP>-induced mitochondrial swelling in hypertrophic hearts
title_short Compensatory role of the NBCn1 sodium/bicarbonate cotransporter on Ca<SUP>2+</SUP>-induced mitochondrial swelling in hypertrophic hearts
title_full Compensatory role of the NBCn1 sodium/bicarbonate cotransporter on Ca<SUP>2+</SUP>-induced mitochondrial swelling in hypertrophic hearts
title_fullStr Compensatory role of the NBCn1 sodium/bicarbonate cotransporter on Ca<SUP>2+</SUP>-induced mitochondrial swelling in hypertrophic hearts
title_full_unstemmed Compensatory role of the NBCn1 sodium/bicarbonate cotransporter on Ca<SUP>2+</SUP>-induced mitochondrial swelling in hypertrophic hearts
title_sort compensatory role of the nbcn1 sodium/bicarbonate cotransporter on ca<sup>2+</sup>-induced mitochondrial swelling in hypertrophic hearts
publishDate 2017
url http://sedici.unlp.edu.ar/handle/10915/102178
https://ri.conicet.gov.ar/11336/54406
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AT carrizovelasquezfernandaelisabeth compensatoryroleofthenbcn1sodiumbicarbonatecotransporteroncasup2supinducedmitochondrialswellinginhypertrophichearts
AT alvarezbernardovictor compensatoryroleofthenbcn1sodiumbicarbonatecotransporteroncasup2supinducedmitochondrialswellinginhypertrophichearts
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