Hetero-oligomerizaciòn entre los receptores Mas de Angiotensina-(1-7) y B2 de Bradikinina : consecuencias funcionales
Bradykinin (BK) B2 receptor (R) and angiotensin (Ang) (1-7) MasR-mediated effects are physiologically interconnected. The molecular basis for such cross-talk is unknown. We investigated B2R-MasR heteromerization and its functional consequences. B2R fused to the cyan fluorescent protein and MasR fuse...
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Formato: | Tesis doctoral acceptedVersion |
Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2018
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Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2768 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2768.dir/2768.PDF |
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I28-R145-HWA_27682020-02-04 Bradykinin (BK) B2 receptor (R) and angiotensin (Ang) (1-7) MasR-mediated effects are physiologically interconnected. The molecular basis for such cross-talk is unknown. We investigated B2R-MasR heteromerization and its functional consequences. B2R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were co-expressed in HEK293T cells. Fluorescence resonance energy transfer (FRET) analysis showed that B2R and MasR formed a constitutive heteromer which was not modified by their agonists but was decreased by the antagonists suggesting heteromer dissociation. B2R-MasR heteromerization induced an increase in the MasR ligand binding affinity. Upon agonist stimulation, the heteromer was internalized with a slower sequestration rate from the plasma membrane compared to the single Rs. Concerning Akt activity, a significant BK promoted activation was detected in B2R-MasR- but not in B2R-expressing cells. Ang-(1-7) and BK elicited anti-proliferative effects only in cells expressing B2R-MasR heteromers but not in cells expressing each R alone. Proximity ligarion assay confirmed B2R-MasR interaction in human glomerular endothelial cells supporting the interaction between both Rs in vivo. Our findings provide an explanation for the cross-talk between BK B2R and Ang-(1-7) MasR mediated effects. B2R-MasR heteromerization induces functional changes in the R that may lead to long-lasting protective properties. Fil: Cerrato, Bruno Diego. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Facultad de Farmacia y Bioquímica Gironacci, Mariela M. Cerrato, Bruno Diego 2018-11-29 Evidencias fisiológicas sugieren una interacción entre el receptor (R) de bradiquinina (BK) B2 y el RMas de angiotensina (Ang) (1-7). La base molecular deelloes desconocida. Investigamos la heteromerización de los RB2 y Mas y sus consecuencias funcionales. El RB2 fusionado a la proteína fluorescente cian y el RMas fusionado a la proteína fluorescente amarilla se expresaron en células HEK293T. El análisis de transferencia de energía de resonancia de fluorescencia mostró que dichos Rsformaron un heterómero constitutivo que no fue modificado por sus agonistas mientras que fue disminuido por los antagonistas de dichos Rs, sugiriendouna disociación. La heteromerización indujo un aumento en la afinidad por el ligando y una tasa de secuestro más lenta desde la membrana plasmática en comparación con los Rs individuales. Respecto a la señalización, se detectó una activación de Aktpromovida por BK solo en células que expresaron el heterómero. Ang-(1-7) y BK provocaron efectos antiproliferativos solo en células que expresaron el heterómeroRB2-RMas, pero no en células que expresaron cada R solo. Confirmamos la interacción RB2-RMas en condiciones nativas. Nuestros hallazgos explican la interacción entre BK y Ang-(1-7). La heteromerizaciónRB2-RMas induce cambios funcionales en los Rs que llevarían a propiedades protectoras de mayor duración. application/pdf Arranz, Cristina Paz, Cristina Ennis, Irene spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Heter-oligomerización Receptores Mas Angiotensina-(1-7) B2 Bradikinina Ciencia de la vida Hetero-oligomerizaciòn entre los receptores Mas de Angiotensina-(1-7) y B2 de Bradikinina : consecuencias funcionales info:eu-repo/semantics/doctoralThesis info:ar-repo/semantics/tesis doctoral info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2768 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2768.dir/2768.PDF |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-145 |
collection |
Repositorio Digital de la Universidad de Buenos Aires (UBA) |
language |
Español |
orig_language_str_mv |
spa |
topic |
Heter-oligomerización Receptores Mas Angiotensina-(1-7) B2 Bradikinina Ciencia de la vida |
spellingShingle |
Heter-oligomerización Receptores Mas Angiotensina-(1-7) B2 Bradikinina Ciencia de la vida Cerrato, Bruno Diego Hetero-oligomerizaciòn entre los receptores Mas de Angiotensina-(1-7) y B2 de Bradikinina : consecuencias funcionales |
topic_facet |
Heter-oligomerización Receptores Mas Angiotensina-(1-7) B2 Bradikinina Ciencia de la vida |
description |
Bradykinin (BK) B2 receptor (R) and angiotensin (Ang) (1-7) MasR-mediated effects are physiologically interconnected. The molecular basis for such cross-talk is unknown. We investigated B2R-MasR heteromerization and its functional consequences. B2R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were co-expressed in HEK293T cells. Fluorescence resonance energy transfer (FRET) analysis showed that B2R and MasR formed a constitutive heteromer which was not modified by their agonists but was decreased by the antagonists suggesting heteromer dissociation. B2R-MasR heteromerization induced an increase in the MasR ligand binding affinity. Upon agonist stimulation, the heteromer was internalized with a slower sequestration rate from the plasma membrane compared to the single Rs. Concerning Akt activity, a significant BK promoted activation was detected in B2R-MasR- but not in B2R-expressing cells. Ang-(1-7) and BK elicited anti-proliferative effects only in cells expressing B2R-MasR heteromers but not in cells expressing each R alone. Proximity ligarion assay confirmed B2R-MasR interaction in human glomerular endothelial cells supporting the interaction between both Rs in vivo. Our findings provide an explanation for the cross-talk between BK B2R and Ang-(1-7) MasR mediated effects. B2R-MasR heteromerization induces functional changes in the R that may lead to long-lasting protective properties. |
author2 |
Gironacci, Mariela M. |
author_facet |
Gironacci, Mariela M. Cerrato, Bruno Diego |
format |
Tesis doctoral Tesis doctoral acceptedVersion |
author |
Cerrato, Bruno Diego |
author_sort |
Cerrato, Bruno Diego |
title |
Hetero-oligomerizaciòn entre los receptores Mas de Angiotensina-(1-7) y B2 de Bradikinina : consecuencias funcionales |
title_short |
Hetero-oligomerizaciòn entre los receptores Mas de Angiotensina-(1-7) y B2 de Bradikinina : consecuencias funcionales |
title_full |
Hetero-oligomerizaciòn entre los receptores Mas de Angiotensina-(1-7) y B2 de Bradikinina : consecuencias funcionales |
title_fullStr |
Hetero-oligomerizaciòn entre los receptores Mas de Angiotensina-(1-7) y B2 de Bradikinina : consecuencias funcionales |
title_full_unstemmed |
Hetero-oligomerizaciòn entre los receptores Mas de Angiotensina-(1-7) y B2 de Bradikinina : consecuencias funcionales |
title_sort |
hetero-oligomerizaciòn entre los receptores mas de angiotensina-(1-7) y b2 de bradikinina : consecuencias funcionales |
publisher |
Facultad de Farmacia y Bioquímica |
publishDate |
2018 |
url |
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2768 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2768.dir/2768.PDF |
work_keys_str_mv |
AT cerratobrunodiego heterooligomerizacionentrelosreceptoresmasdeangiotensina17yb2debradikininaconsecuenciasfuncionales |
_version_ |
1766017511892975616 |