CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
artículos
Título:
Reduced sarcolemmal expression and function of the NBCe1 isoform of the Na+/HCO3- cotransporter in hypertrophied cardiomyocytes of spontaneously hypertensive rats: role of the renin-angiotensin system.
Autor/es:
ORLOWSKI A; CIANCIO MC; CALDIZ CI; DE GIUSTI VC; AIELLO EA
Revista:
CARDIOVASCULAR RESEARCH
Editorial:
OXFORD UNIV PRESS
Referencias:
Lugar: Oxford; Año: 2014 vol. 101 p. 211 - 219
ISSN:
0008-6363
Resumen:
Aims Electroneutral (NBCn1) and electrogenic (NBCe1) isoforms of the Na+?HCO−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.
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.
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.
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.
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.
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 over-expression 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 IIinduced
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.
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.
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.
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.
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.
NBCe1 expression, its activity was lower in SHR than in Wistar or Los-SHR. Similar results were found in Ang IIinduced
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.
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.
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.
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.
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.
NBCe1 expression, its activity was lower in SHR than in Wistar or Los-SHR. Similar results were found in Ang IIinduced
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.
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.
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.
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.
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.
NBCe1 expression, its activity was lower in SHR than in Wistar or Los-SHR. Similar results were found in Ang IIinduced
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.
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.
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.
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.
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.
NBCe1 expression, its activity was lower in SHR than in Wistar or Los-SHR. Similar results were found in Ang IIinduced
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.
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.
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.
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.
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.
i 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 IIinduced
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.
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.
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.
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.
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.
i 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,NBCn1activity seems to be increased in the hypertrophic myocardium
of SHR, compensating impaired function of NBCe1.
transporter protein units in early endosomes. Moreover,NBCn1activity seems to be increased in the hypertrophic myocardium
of SHR, compensating impaired function of NBCe1.
transporter protein units in early endosomes. Moreover,NBCn1activity seems to be increased in the hypertrophic myocardium
of SHR, compensating impaired function of NBCe1.
transporter protein units in early endosomes. Moreover,NBCn1activity seems to be increased in the hypertrophic myocardium
of SHR, compensating impaired function of NBCe1.
transporter protein units in early endosomes. Moreover,NBCn1activity seems to be increased in the hypertrophic myocardium
of SHR, compensating impaired function of NBCe1.
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,NBCn1activity seems to be increased in the hypertrophic myocardium
of SHR, compensating impaired function of NBCe1.