Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the reni...

Autores
Orlowski, Alejandro; Ciancio, María Carolina; Caldiz, Claudia Irma; De Giusti, Verónica Celeste; Aiello, Ernesto Alejandro
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Aims. Electroneutral (NBCn1) and electrogenic (NBCe1) isoforms of the Na+‒HCO¯3 cotransporter (NBC) coexist in the heart. We studied the expression and function of these isoforms in hearts of Wistar and spontaneously hypertensive rats (SHR), elucidating the direct implication of the renin-angiotensin system in the NBC regulation. Methods and results. We used myocytes from Wistar, SHR, losartan-treated SHR (Los-SHR), and Angiotensin II (Ang II)-induced cardiac hypertrophy. We found an overexpression of NBCe1 and NBCn1 proteins in SHR that was prevented in Los-SHR. Hyperkalaemic-induced pHi alkalization was used to study selective activation of NBCe1. Despite the increase in NBCe1 expression, its activity was lower in SHR than in Wistar or Los-SHR. Similar results were found in Ang II-induced hypertrophy. A specific inhibitory antibody against NBCe1 allowed the discrimination between NBCe1 and NBCn1 activity. Whereas in SHR most of the pHi recovery was due to NBCn1 stimulation, in Wistar and Los-SHR the activity of both isoforms was equitable, suggesting that the deteriorated cardiac NBCe1 function observed in SHR is compensated by an enhanced activity of NBCn1. Using the biotin method, we observed greater level of internalized NBCe1 protein in SHR than in the non-hypertophic groups, while with immunofluorescence we localized the protein in endosomes near the nucleus only in SHR. Conclusions. We conclude that Ang II is responsible for the impairment of the NBCe1 in hypertrophied hearts. This is due to retained transporter protein units in early endosomes. Moreover, NBCn1 activity seems to be increased in the hypertrophic myocardium of SHR, compensating impaired function of NBCe1.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
Materia
Ciencias Médicas
Cardiac hypertrophy
Cardiac myocytes
Na+‒HCO¯3 cotransporter
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/85081
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/85081
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the renin-angiotensin systemOrlowski, AlejandroCiancio, María CarolinaCaldiz, Claudia IrmaDe Giusti, Verónica CelesteAiello, Ernesto AlejandroCiencias MédicasCardiac hypertrophyCardiac myocytesNa+‒HCO¯3 cotransporterAims. Electroneutral (NBCn1) and electrogenic (NBCe1) isoforms of the Na<SUP>+</SUP>‒HCO¯<SUB>3</SUB> cotransporter (NBC) coexist in the heart. We studied the expression and function of these isoforms in hearts of Wistar and spontaneously hypertensive rats (SHR), elucidating the direct implication of the renin-angiotensin system in the NBC regulation. Methods and results. We used myocytes from Wistar, SHR, losartan-treated SHR (Los-SHR), and Angiotensin II (Ang II)-induced cardiac hypertrophy. We found an overexpression of NBCe1 and NBCn1 proteins in SHR that was prevented in Los-SHR. Hyperkalaemic-induced pHi alkalization was used to study selective activation of NBCe1. Despite the increase in NBCe1 expression, its activity was lower in SHR than in Wistar or Los-SHR. Similar results were found in Ang II-induced hypertrophy. A specific inhibitory antibody against NBCe1 allowed the discrimination between NBCe1 and NBCn1 activity. Whereas in SHR most of the pHi recovery was due to NBCn1 stimulation, in Wistar and Los-SHR the activity of both isoforms was equitable, suggesting that the deteriorated cardiac NBCe1 function observed in SHR is compensated by an enhanced activity of NBCn1. Using the biotin method, we observed greater level of internalized NBCe1 protein in SHR than in the non-hypertophic groups, while with immunofluorescence we localized the protein in endosomes near the nucleus only in SHR. Conclusions. We conclude that Ang II is responsible for the impairment of the NBCe1 in hypertrophied hearts. This is due to retained transporter protein units in early endosomes. Moreover, NBCn1 activity seems to be increased in the hypertrophic myocardium of SHR, compensating impaired function of NBCe1.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculares2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf211-219http://sedici.unlp.edu.ar/handle/10915/85081enginfo:eu-repo/semantics/altIdentifier/issn/0008-6363info:eu-repo/semantics/altIdentifier/doi/10.1093/cvr/cvt255info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-03T10:48:41Zoai:sedici.unlp.edu.ar:10915/85081Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-03 10:48:41.355SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the renin-angiotensin system
title Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the renin-angiotensin system
spellingShingle Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the renin-angiotensin system
Orlowski, Alejandro
Ciencias Médicas
Cardiac hypertrophy
Cardiac myocytes
Na+‒HCO¯3 cotransporter
title_short Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the renin-angiotensin system
title_full Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the renin-angiotensin system
title_fullStr Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the renin-angiotensin system
title_full_unstemmed Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the renin-angiotensin system
title_sort Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+‒HCO¯3 cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: Role of the renin-angiotensin system
dc.creator.none.fl_str_mv Orlowski, Alejandro
Ciancio, María Carolina
Caldiz, Claudia Irma
De Giusti, Verónica Celeste
Aiello, Ernesto Alejandro
author Orlowski, Alejandro
author_facet Orlowski, Alejandro
Ciancio, María Carolina
Caldiz, Claudia Irma
De Giusti, Verónica Celeste
Aiello, Ernesto Alejandro
author_role author
author2 Ciancio, María Carolina
Caldiz, Claudia Irma
De Giusti, Verónica Celeste
Aiello, Ernesto Alejandro
author2_role author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Cardiac hypertrophy
Cardiac myocytes
Na+‒HCO¯3 cotransporter
topic Ciencias Médicas
Cardiac hypertrophy
Cardiac myocytes
Na+‒HCO¯3 cotransporter
dc.description.none.fl_txt_mv Aims. Electroneutral (NBCn1) and electrogenic (NBCe1) isoforms of the Na<SUP>+</SUP>‒HCO¯<SUB>3</SUB> cotransporter (NBC) coexist in the heart. We studied the expression and function of these isoforms in hearts of Wistar and spontaneously hypertensive rats (SHR), elucidating the direct implication of the renin-angiotensin system in the NBC regulation. Methods and results. We used myocytes from Wistar, SHR, losartan-treated SHR (Los-SHR), and Angiotensin II (Ang II)-induced cardiac hypertrophy. We found an overexpression of NBCe1 and NBCn1 proteins in SHR that was prevented in Los-SHR. Hyperkalaemic-induced pHi alkalization was used to study selective activation of NBCe1. Despite the increase in NBCe1 expression, its activity was lower in SHR than in Wistar or Los-SHR. Similar results were found in Ang II-induced hypertrophy. A specific inhibitory antibody against NBCe1 allowed the discrimination between NBCe1 and NBCn1 activity. Whereas in SHR most of the pHi recovery was due to NBCn1 stimulation, in Wistar and Los-SHR the activity of both isoforms was equitable, suggesting that the deteriorated cardiac NBCe1 function observed in SHR is compensated by an enhanced activity of NBCn1. Using the biotin method, we observed greater level of internalized NBCe1 protein in SHR than in the non-hypertophic groups, while with immunofluorescence we localized the protein in endosomes near the nucleus only in SHR. Conclusions. We conclude that Ang II is responsible for the impairment of the NBCe1 in hypertrophied hearts. This is due to retained transporter protein units in early endosomes. Moreover, NBCn1 activity seems to be increased in the hypertrophic myocardium of SHR, compensating impaired function of NBCe1.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares
description Aims. Electroneutral (NBCn1) and electrogenic (NBCe1) isoforms of the Na<SUP>+</SUP>‒HCO¯<SUB>3</SUB> cotransporter (NBC) coexist in the heart. We studied the expression and function of these isoforms in hearts of Wistar and spontaneously hypertensive rats (SHR), elucidating the direct implication of the renin-angiotensin system in the NBC regulation. Methods and results. We used myocytes from Wistar, SHR, losartan-treated SHR (Los-SHR), and Angiotensin II (Ang II)-induced cardiac hypertrophy. We found an overexpression of NBCe1 and NBCn1 proteins in SHR that was prevented in Los-SHR. Hyperkalaemic-induced pHi alkalization was used to study selective activation of NBCe1. Despite the increase in NBCe1 expression, its activity was lower in SHR than in Wistar or Los-SHR. Similar results were found in Ang II-induced hypertrophy. A specific inhibitory antibody against NBCe1 allowed the discrimination between NBCe1 and NBCn1 activity. Whereas in SHR most of the pHi recovery was due to NBCn1 stimulation, in Wistar and Los-SHR the activity of both isoforms was equitable, suggesting that the deteriorated cardiac NBCe1 function observed in SHR is compensated by an enhanced activity of NBCn1. Using the biotin method, we observed greater level of internalized NBCe1 protein in SHR than in the non-hypertophic groups, while with immunofluorescence we localized the protein in endosomes near the nucleus only in SHR. Conclusions. We conclude that Ang II is responsible for the impairment of the NBCe1 in hypertrophied hearts. This is due to retained transporter protein units in early endosomes. Moreover, NBCn1 activity seems to be increased in the hypertrophic myocardium of SHR, compensating impaired function of NBCe1.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/85081
url http://sedici.unlp.edu.ar/handle/10915/85081
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0008-6363
info:eu-repo/semantics/altIdentifier/doi/10.1093/cvr/cvt255
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
211-219
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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