Tráfico del receptor Mas, un receptor asociado a respuestas protectoras y anti-hipertensivas, en la hipertensión arterial
Mas receptor (MasR) is a G-protein-coupled receptor. Receptor trafficking has critical function in signal termination, propagation and resensitization. The objective of the present work is to investigate MasR trafficking in physiological and pathological situations as in hypertension. We examined Ma...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2017
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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_1977 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1977.dir/1977.PDF |
| Aporte de: |
| Sumario: | Mas receptor (MasR) is a G-protein-coupled receptor. Receptor trafficking has critical function in signal termination, propagation and resensitization. The objective of the present work is to investigate MasR trafficking in physiological and pathological situations as in hypertension. We examined MasR internalization and trafficking after agonist stimulation in human embryonic kidney 293T (HEK293T) cells and in brainstem neurons from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). We also evaluated the role of ?-arrestin2 in the activation of ERK1/2 and Akt after MasR stimulation in HEK293T cells. We demonstrated that MasR is internalized through clathrin-coated pits and caveolae and is then slowly recycled back to the plasma membrane in HEK293T cells and in neurons from both strains. However, MasR displays a differential trafficking in neurons from SHR: a greater fraction of MasR is internalized, a decreased fraction is recycled back to the plasma membrane and a fraction is translocated to the nucleus. We also demonstrated that MasR induces Akt and ERK1/2 activation from early endosomes, and that the activation of ERK1/2 is mediated by ?-arrestin2. Thus, MasR activity and density may be tightly controlled by the cell and alterations in MasR trafficking could be involved in the development of hypertension. |
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