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(-)-Epicatechin Is a Biased Ligand of Apelin Receptor

(-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids and is widely distributed in the plant kingdom. Several studies have shown the beneficial effects of EC consumption. Many of these reported effects are exerted by activating the signaling pathways associated with the ac...

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Autores principales: Portilla-Martínez, Andrés, Ortiz-Flores, Miguel Ángel, Meaney, Eduardo, Villarreal, Francisco, Nájera, Nayelli, Ceballos, Guillermo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409145/
https://www.ncbi.nlm.nih.gov/pubmed/36012227
http://dx.doi.org/10.3390/ijms23168962
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author Portilla-Martínez, Andrés
Ortiz-Flores, Miguel Ángel
Meaney, Eduardo
Villarreal, Francisco
Nájera, Nayelli
Ceballos, Guillermo
author_facet Portilla-Martínez, Andrés
Ortiz-Flores, Miguel Ángel
Meaney, Eduardo
Villarreal, Francisco
Nájera, Nayelli
Ceballos, Guillermo
author_sort Portilla-Martínez, Andrés
collection PubMed
description (-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids and is widely distributed in the plant kingdom. Several studies have shown the beneficial effects of EC consumption. Many of these reported effects are exerted by activating the signaling pathways associated with the activation of two specific receptors: the G protein-coupled estrogen receptor (GPER), a transmembrane receptor, and the pregnane X receptor (PXR), which is a nuclear receptor. However, the effects of EC are so diverse that these two receptors cannot describe the complete phenomenon. The apelin receptor or APLNR is classified within the G protein-coupled receptor (GPCR) family, and is capable of activating the G protein canonical pathways and the β-arrestin transducer, which participates in the phenomenon of receptor desensitization and internalization. β-arrestin gained interest in selective pharmacology and mediators of the so-called “biased agonism”. With molecular dynamics (MD) and in vitro assays, we demonstrate how EC can recruit the β-arrestin in the active conformation of the APLN receptor acting as a biased agonist.
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spelling pubmed-94091452022-08-26 (-)-Epicatechin Is a Biased Ligand of Apelin Receptor Portilla-Martínez, Andrés Ortiz-Flores, Miguel Ángel Meaney, Eduardo Villarreal, Francisco Nájera, Nayelli Ceballos, Guillermo Int J Mol Sci Article (-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids and is widely distributed in the plant kingdom. Several studies have shown the beneficial effects of EC consumption. Many of these reported effects are exerted by activating the signaling pathways associated with the activation of two specific receptors: the G protein-coupled estrogen receptor (GPER), a transmembrane receptor, and the pregnane X receptor (PXR), which is a nuclear receptor. However, the effects of EC are so diverse that these two receptors cannot describe the complete phenomenon. The apelin receptor or APLNR is classified within the G protein-coupled receptor (GPCR) family, and is capable of activating the G protein canonical pathways and the β-arrestin transducer, which participates in the phenomenon of receptor desensitization and internalization. β-arrestin gained interest in selective pharmacology and mediators of the so-called “biased agonism”. With molecular dynamics (MD) and in vitro assays, we demonstrate how EC can recruit the β-arrestin in the active conformation of the APLN receptor acting as a biased agonist. MDPI 2022-08-11 /pmc/articles/PMC9409145/ /pubmed/36012227 http://dx.doi.org/10.3390/ijms23168962 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Portilla-Martínez, Andrés
Ortiz-Flores, Miguel Ángel
Meaney, Eduardo
Villarreal, Francisco
Nájera, Nayelli
Ceballos, Guillermo
(-)-Epicatechin Is a Biased Ligand of Apelin Receptor
title (-)-Epicatechin Is a Biased Ligand of Apelin Receptor
title_full (-)-Epicatechin Is a Biased Ligand of Apelin Receptor
title_fullStr (-)-Epicatechin Is a Biased Ligand of Apelin Receptor
title_full_unstemmed (-)-Epicatechin Is a Biased Ligand of Apelin Receptor
title_short (-)-Epicatechin Is a Biased Ligand of Apelin Receptor
title_sort (-)-epicatechin is a biased ligand of apelin receptor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409145/
https://www.ncbi.nlm.nih.gov/pubmed/36012227
http://dx.doi.org/10.3390/ijms23168962
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