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Endothelin-1 induces cellular senescence and fibrosis in cultured myoblasts. A potential mechanism of aging-related sarcopenia

Endothelial dysfunction, with increased endothelin-1 (ET-1) synthesis, and sarcopenia, characterized by the loss of muscular mass and strength, are two aging–related conditions. However, a relationship between them has not been already established. The aim of this study was to determine whether ET-1...

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Autores principales: Alcalde-Estévez, Elena, Asenjo-Bueno, Ana, Sosa, Patricia, Olmos, Gemma, Plaza, Patricia, Caballero-Mora, María Ángeles, Rodríguez-Puyol, Diego, Ruíz-Torres, María Piedad, López-Ongil, Susana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343454/
https://www.ncbi.nlm.nih.gov/pubmed/32572011
http://dx.doi.org/10.18632/aging.103450
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author Alcalde-Estévez, Elena
Asenjo-Bueno, Ana
Sosa, Patricia
Olmos, Gemma
Plaza, Patricia
Caballero-Mora, María Ángeles
Rodríguez-Puyol, Diego
Ruíz-Torres, María Piedad
López-Ongil, Susana
author_facet Alcalde-Estévez, Elena
Asenjo-Bueno, Ana
Sosa, Patricia
Olmos, Gemma
Plaza, Patricia
Caballero-Mora, María Ángeles
Rodríguez-Puyol, Diego
Ruíz-Torres, María Piedad
López-Ongil, Susana
author_sort Alcalde-Estévez, Elena
collection PubMed
description Endothelial dysfunction, with increased endothelin-1 (ET-1) synthesis, and sarcopenia, characterized by the loss of muscular mass and strength, are two aging–related conditions. However, a relationship between them has not been already established. The aim of this study was to determine whether ET-1 induces senescence and fibrosis in cultured murine myoblasts, which could be involved in the development of sarcopenia related to aging. For this purpose, myoblasts were incubated with ET-1 to assess cellular senescence, analyzed by senescence associated β-galactosidase activity and p16 expression; and fibrosis, assessed by fibronectin expression. ET-1 induced myoblast senescence and fibrosis through ET(A) receptor. The use of antioxidants and several antagonists revealed that ET-1 effect on senescence and fibrosis depended on ROS production and activation of PI(3)K-AKT-GSK pathway. To stress the in vivo relevance of these results, circulating ET-1, muscular strength, muscular fibrosis and p16 expression were measured in male C57Bl6 mice from 5-18-24-months-old. Old mice shown high levels of ET-1 correlated with muscular fibrosis, muscular p16 expression and loss of muscle strength. In conclusion, ET-1 promotes fibrosis and senescence in cultured myoblasts, similar results were found in old mice, suggesting a potential role for ET-1 in the development of sarcopenia related to aging.
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spelling pubmed-73434542020-07-15 Endothelin-1 induces cellular senescence and fibrosis in cultured myoblasts. A potential mechanism of aging-related sarcopenia Alcalde-Estévez, Elena Asenjo-Bueno, Ana Sosa, Patricia Olmos, Gemma Plaza, Patricia Caballero-Mora, María Ángeles Rodríguez-Puyol, Diego Ruíz-Torres, María Piedad López-Ongil, Susana Aging (Albany NY) Priority Research Paper Endothelial dysfunction, with increased endothelin-1 (ET-1) synthesis, and sarcopenia, characterized by the loss of muscular mass and strength, are two aging–related conditions. However, a relationship between them has not been already established. The aim of this study was to determine whether ET-1 induces senescence and fibrosis in cultured murine myoblasts, which could be involved in the development of sarcopenia related to aging. For this purpose, myoblasts were incubated with ET-1 to assess cellular senescence, analyzed by senescence associated β-galactosidase activity and p16 expression; and fibrosis, assessed by fibronectin expression. ET-1 induced myoblast senescence and fibrosis through ET(A) receptor. The use of antioxidants and several antagonists revealed that ET-1 effect on senescence and fibrosis depended on ROS production and activation of PI(3)K-AKT-GSK pathway. To stress the in vivo relevance of these results, circulating ET-1, muscular strength, muscular fibrosis and p16 expression were measured in male C57Bl6 mice from 5-18-24-months-old. Old mice shown high levels of ET-1 correlated with muscular fibrosis, muscular p16 expression and loss of muscle strength. In conclusion, ET-1 promotes fibrosis and senescence in cultured myoblasts, similar results were found in old mice, suggesting a potential role for ET-1 in the development of sarcopenia related to aging. Impact Journals 2020-06-22 /pmc/articles/PMC7343454/ /pubmed/32572011 http://dx.doi.org/10.18632/aging.103450 Text en Copyright © 2020 Alcalde-Estévez et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Priority Research Paper
Alcalde-Estévez, Elena
Asenjo-Bueno, Ana
Sosa, Patricia
Olmos, Gemma
Plaza, Patricia
Caballero-Mora, María Ángeles
Rodríguez-Puyol, Diego
Ruíz-Torres, María Piedad
López-Ongil, Susana
Endothelin-1 induces cellular senescence and fibrosis in cultured myoblasts. A potential mechanism of aging-related sarcopenia
title Endothelin-1 induces cellular senescence and fibrosis in cultured myoblasts. A potential mechanism of aging-related sarcopenia
title_full Endothelin-1 induces cellular senescence and fibrosis in cultured myoblasts. A potential mechanism of aging-related sarcopenia
title_fullStr Endothelin-1 induces cellular senescence and fibrosis in cultured myoblasts. A potential mechanism of aging-related sarcopenia
title_full_unstemmed Endothelin-1 induces cellular senescence and fibrosis in cultured myoblasts. A potential mechanism of aging-related sarcopenia
title_short Endothelin-1 induces cellular senescence and fibrosis in cultured myoblasts. A potential mechanism of aging-related sarcopenia
title_sort endothelin-1 induces cellular senescence and fibrosis in cultured myoblasts. a potential mechanism of aging-related sarcopenia
topic Priority Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343454/
https://www.ncbi.nlm.nih.gov/pubmed/32572011
http://dx.doi.org/10.18632/aging.103450
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