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Filamin A cooperates with the androgen receptor in preventing skeletal muscle senescence

Aging induces a slow and progressive decrease in muscle mass and function, causing sarcopenia. Androgens control muscle trophism and exert important anabolic functions through the binding to the androgen receptor. Therefore, analysis of the androgen receptor-mediated actions in skeletal muscle might...

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Autores principales: Di Donato, Marzia, Moretti, Antimo, Sorrentino, Carmela, Toro, Giuseppe, Gentile, Giulia, Iolascon, Giovanni, Castoria, Gabriella, Migliaccio, Antimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692324/
https://www.ncbi.nlm.nih.gov/pubmed/38040692
http://dx.doi.org/10.1038/s41420-023-01737-y
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author Di Donato, Marzia
Moretti, Antimo
Sorrentino, Carmela
Toro, Giuseppe
Gentile, Giulia
Iolascon, Giovanni
Castoria, Gabriella
Migliaccio, Antimo
author_facet Di Donato, Marzia
Moretti, Antimo
Sorrentino, Carmela
Toro, Giuseppe
Gentile, Giulia
Iolascon, Giovanni
Castoria, Gabriella
Migliaccio, Antimo
author_sort Di Donato, Marzia
collection PubMed
description Aging induces a slow and progressive decrease in muscle mass and function, causing sarcopenia. Androgens control muscle trophism and exert important anabolic functions through the binding to the androgen receptor. Therefore, analysis of the androgen receptor-mediated actions in skeletal muscle might provide new hints for a better understanding of sarcopenia pathogenesis. In this study, we report that expression of the androgen receptor in skeletal muscle biopsies from 20 subjects is higher in young, as compared with old subjects. Co-immunoprecipitation experiments reveal that the androgen receptor is complexed with filamin A mainly in young, that in old subjects. Therefore, we have in depth analyzed the role of such complex using C2C12 myoblasts that express a significant amount of the androgen receptor. In these cells, hormone stimulation rapidly triggers the assembly of the androgen receptor/filamin A complex. Such complex prevents the senescence induced by oxidative stress in C2C12 cells, as disruption of the androgen receptor/filamin A complex by Rh-2025u stapled peptide re-establishes the senescent phenotype in C2C12 cells. Simultaneously, androgen stimulation of C2C12 cells rapidly triggers the activation of various signaling effectors, including Rac1, focal adhesion kinase, and mitogen-activated kinases. Androgen receptor blockade by bicalutamide or perturbation of androgen receptor/filamin A complex by Rh-2025u stapled peptide both reverse the hormone activation of signaling effectors. These findings further reinforce the role of the androgen receptor and its extranuclear partners in the rapid hormone signaling that controls the functions of C2C12 cells. Further investigations are needed to promote clinical interventions that might ameliorate muscle cell function as well the clinical outcome of age-related frailty.
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spelling pubmed-106923242023-12-03 Filamin A cooperates with the androgen receptor in preventing skeletal muscle senescence Di Donato, Marzia Moretti, Antimo Sorrentino, Carmela Toro, Giuseppe Gentile, Giulia Iolascon, Giovanni Castoria, Gabriella Migliaccio, Antimo Cell Death Discov Article Aging induces a slow and progressive decrease in muscle mass and function, causing sarcopenia. Androgens control muscle trophism and exert important anabolic functions through the binding to the androgen receptor. Therefore, analysis of the androgen receptor-mediated actions in skeletal muscle might provide new hints for a better understanding of sarcopenia pathogenesis. In this study, we report that expression of the androgen receptor in skeletal muscle biopsies from 20 subjects is higher in young, as compared with old subjects. Co-immunoprecipitation experiments reveal that the androgen receptor is complexed with filamin A mainly in young, that in old subjects. Therefore, we have in depth analyzed the role of such complex using C2C12 myoblasts that express a significant amount of the androgen receptor. In these cells, hormone stimulation rapidly triggers the assembly of the androgen receptor/filamin A complex. Such complex prevents the senescence induced by oxidative stress in C2C12 cells, as disruption of the androgen receptor/filamin A complex by Rh-2025u stapled peptide re-establishes the senescent phenotype in C2C12 cells. Simultaneously, androgen stimulation of C2C12 cells rapidly triggers the activation of various signaling effectors, including Rac1, focal adhesion kinase, and mitogen-activated kinases. Androgen receptor blockade by bicalutamide or perturbation of androgen receptor/filamin A complex by Rh-2025u stapled peptide both reverse the hormone activation of signaling effectors. These findings further reinforce the role of the androgen receptor and its extranuclear partners in the rapid hormone signaling that controls the functions of C2C12 cells. Further investigations are needed to promote clinical interventions that might ameliorate muscle cell function as well the clinical outcome of age-related frailty. Nature Publishing Group UK 2023-12-02 /pmc/articles/PMC10692324/ /pubmed/38040692 http://dx.doi.org/10.1038/s41420-023-01737-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Di Donato, Marzia
Moretti, Antimo
Sorrentino, Carmela
Toro, Giuseppe
Gentile, Giulia
Iolascon, Giovanni
Castoria, Gabriella
Migliaccio, Antimo
Filamin A cooperates with the androgen receptor in preventing skeletal muscle senescence
title Filamin A cooperates with the androgen receptor in preventing skeletal muscle senescence
title_full Filamin A cooperates with the androgen receptor in preventing skeletal muscle senescence
title_fullStr Filamin A cooperates with the androgen receptor in preventing skeletal muscle senescence
title_full_unstemmed Filamin A cooperates with the androgen receptor in preventing skeletal muscle senescence
title_short Filamin A cooperates with the androgen receptor in preventing skeletal muscle senescence
title_sort filamin a cooperates with the androgen receptor in preventing skeletal muscle senescence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692324/
https://www.ncbi.nlm.nih.gov/pubmed/38040692
http://dx.doi.org/10.1038/s41420-023-01737-y
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