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Master Regulators of Muscle Atrophy: Role of Costamere Components

The loss of muscle mass and force characterizes muscle atrophy in several different conditions, which share the expression of atrogenes and the activation of their transcriptional regulators. However, attempts to antagonize muscle atrophy development in different experimental contexts by targeting c...

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Detalles Bibliográficos
Autores principales: Gorza, Luisa, Sorge, Matteo, Seclì, Laura, Brancaccio, Mara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823551/
https://www.ncbi.nlm.nih.gov/pubmed/33401549
http://dx.doi.org/10.3390/cells10010061
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author Gorza, Luisa
Sorge, Matteo
Seclì, Laura
Brancaccio, Mara
author_facet Gorza, Luisa
Sorge, Matteo
Seclì, Laura
Brancaccio, Mara
author_sort Gorza, Luisa
collection PubMed
description The loss of muscle mass and force characterizes muscle atrophy in several different conditions, which share the expression of atrogenes and the activation of their transcriptional regulators. However, attempts to antagonize muscle atrophy development in different experimental contexts by targeting contributors to the atrogene pathway showed partial effects in most cases. Other master regulators might independently contribute to muscle atrophy, as suggested by our recent evidence about the co-requirement of the muscle-specific chaperone protein melusin to inhibit unloading muscle atrophy development. Furthermore, melusin and other muscle mass regulators, such as nNOS, belong to costameres, the macromolecular complexes that connect sarcolemma to myofibrils and to the extracellular matrix, in correspondence with specific sarcomeric sites. Costameres sense a mechanical load and transduce it both as lateral force and biochemical signals. Recent evidence further broadens this classic view, by revealing the crucial participation of costameres in a sarcolemmal “signaling hub” integrating mechanical and humoral stimuli, where mechanical signals are coupled with insulin and/or insulin-like growth factor stimulation to regulate muscle mass. Therefore, this review aims to enucleate available evidence concerning the early involvement of costamere components and additional putative master regulators in the development of major types of muscle atrophy.
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spelling pubmed-78235512021-01-24 Master Regulators of Muscle Atrophy: Role of Costamere Components Gorza, Luisa Sorge, Matteo Seclì, Laura Brancaccio, Mara Cells Review The loss of muscle mass and force characterizes muscle atrophy in several different conditions, which share the expression of atrogenes and the activation of their transcriptional regulators. However, attempts to antagonize muscle atrophy development in different experimental contexts by targeting contributors to the atrogene pathway showed partial effects in most cases. Other master regulators might independently contribute to muscle atrophy, as suggested by our recent evidence about the co-requirement of the muscle-specific chaperone protein melusin to inhibit unloading muscle atrophy development. Furthermore, melusin and other muscle mass regulators, such as nNOS, belong to costameres, the macromolecular complexes that connect sarcolemma to myofibrils and to the extracellular matrix, in correspondence with specific sarcomeric sites. Costameres sense a mechanical load and transduce it both as lateral force and biochemical signals. Recent evidence further broadens this classic view, by revealing the crucial participation of costameres in a sarcolemmal “signaling hub” integrating mechanical and humoral stimuli, where mechanical signals are coupled with insulin and/or insulin-like growth factor stimulation to regulate muscle mass. Therefore, this review aims to enucleate available evidence concerning the early involvement of costamere components and additional putative master regulators in the development of major types of muscle atrophy. MDPI 2021-01-03 /pmc/articles/PMC7823551/ /pubmed/33401549 http://dx.doi.org/10.3390/cells10010061 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gorza, Luisa
Sorge, Matteo
Seclì, Laura
Brancaccio, Mara
Master Regulators of Muscle Atrophy: Role of Costamere Components
title Master Regulators of Muscle Atrophy: Role of Costamere Components
title_full Master Regulators of Muscle Atrophy: Role of Costamere Components
title_fullStr Master Regulators of Muscle Atrophy: Role of Costamere Components
title_full_unstemmed Master Regulators of Muscle Atrophy: Role of Costamere Components
title_short Master Regulators of Muscle Atrophy: Role of Costamere Components
title_sort master regulators of muscle atrophy: role of costamere components
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823551/
https://www.ncbi.nlm.nih.gov/pubmed/33401549
http://dx.doi.org/10.3390/cells10010061
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