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
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...
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| Autores principales: | , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
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2014
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/85081 |
| Aporte de: |
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I19-R120-10915-85081 |
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dspace |
| institution |
Universidad Nacional de La Plata |
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I-19 |
| repository_str |
R-120 |
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SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Médicas Cardiac hypertrophy Cardiac myocytes Na+‒HCO¯3 cotransporter |
| spellingShingle |
Ciencias Médicas Cardiac hypertrophy Cardiac myocytes Na+‒HCO¯3 cotransporter Orlowski, Alejandro Ciancio, María Carolina Caldiz, Claudia Irma De Giusti, Verónica Celeste Aiello, Ernesto Alejandro 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 |
| topic_facet |
Ciencias Médicas Cardiac hypertrophy Cardiac myocytes Na+‒HCO¯3 cotransporter |
| 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. |
| format |
Articulo Articulo |
| author |
Orlowski, Alejandro Ciancio, María Carolina Caldiz, Claudia Irma De Giusti, Verónica Celeste Aiello, Ernesto Alejandro |
| author_facet |
Orlowski, Alejandro Ciancio, María Carolina Caldiz, Claudia Irma De Giusti, Verónica Celeste Aiello, Ernesto Alejandro |
| author_sort |
Orlowski, Alejandro |
| 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 |
| 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 |
| publishDate |
2014 |
| url |
http://sedici.unlp.edu.ar/handle/10915/85081 |
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