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UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment

Skeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that ta...

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Autores principales: Cécile, Polge, Julien, Aniort, Andrea, Armani, Agnès, Claustre, Cécile, Coudy-Gandilhon, Clara, Tournebize, Christiane, Deval, Lydie, Combaret, Daniel, Béchet, Marco, Sandri, Didier, Attaix, Daniel, Taillandier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262581/
https://www.ncbi.nlm.nih.gov/pubmed/30453501
http://dx.doi.org/10.3390/cells7110214
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author Cécile, Polge
Julien, Aniort
Andrea, Armani
Agnès, Claustre
Cécile, Coudy-Gandilhon
Clara, Tournebize
Christiane, Deval
Lydie, Combaret
Daniel, Béchet
Marco, Sandri
Didier, Attaix
Daniel, Taillandier
author_facet Cécile, Polge
Julien, Aniort
Andrea, Armani
Agnès, Claustre
Cécile, Coudy-Gandilhon
Clara, Tournebize
Christiane, Deval
Lydie, Combaret
Daniel, Béchet
Marco, Sandri
Didier, Attaix
Daniel, Taillandier
author_sort Cécile, Polge
collection PubMed
description Skeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that target their dedicated substrates for subsequent degradation. We recently demonstrated that MuRF1, an E3 ubiquitin ligase known to bind to sarcomeric proteins (telethonin, α-actin, myosins) during catabolic situations, interacts with 5 different E2 enzymes and that these E2-MuRF1 couples are able to target telethonin, a small sarcomeric protein, for degradation. Amongst the E2s interacting with MuRF1, E2E1 was peculiar as the presence of the substrate was necessary for optimal MuRF1-E2E1 interaction. In this work, we focused on the putative role of E2E1 during skeletal muscle atrophy. We found that E2E1 expression was restricted to type I and type IIA muscle fibers and was not detectable in type IIB fibers. This strongly suggests that E2E1 targets are fiber-specific and may be strongly linked to the contractile and metabolic properties of the skeletal muscle. However, E2E1 knockdown was not sufficient for preserving the protein content in C2C12 myotubes subjected to a catabolic state (dexamethasone treatment), suggesting that E2E1 is not involved in the development of muscle atrophy. By contrast, E2E1 knockdown aggravated the atrophying process in both catabolic C2C12 myotubes and the Tibialis anterior muscle of mice, suggesting that E2E1 has a protective effect on muscle mass.
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spelling pubmed-62625812018-12-03 UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment Cécile, Polge Julien, Aniort Andrea, Armani Agnès, Claustre Cécile, Coudy-Gandilhon Clara, Tournebize Christiane, Deval Lydie, Combaret Daniel, Béchet Marco, Sandri Didier, Attaix Daniel, Taillandier Cells Article Skeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that target their dedicated substrates for subsequent degradation. We recently demonstrated that MuRF1, an E3 ubiquitin ligase known to bind to sarcomeric proteins (telethonin, α-actin, myosins) during catabolic situations, interacts with 5 different E2 enzymes and that these E2-MuRF1 couples are able to target telethonin, a small sarcomeric protein, for degradation. Amongst the E2s interacting with MuRF1, E2E1 was peculiar as the presence of the substrate was necessary for optimal MuRF1-E2E1 interaction. In this work, we focused on the putative role of E2E1 during skeletal muscle atrophy. We found that E2E1 expression was restricted to type I and type IIA muscle fibers and was not detectable in type IIB fibers. This strongly suggests that E2E1 targets are fiber-specific and may be strongly linked to the contractile and metabolic properties of the skeletal muscle. However, E2E1 knockdown was not sufficient for preserving the protein content in C2C12 myotubes subjected to a catabolic state (dexamethasone treatment), suggesting that E2E1 is not involved in the development of muscle atrophy. By contrast, E2E1 knockdown aggravated the atrophying process in both catabolic C2C12 myotubes and the Tibialis anterior muscle of mice, suggesting that E2E1 has a protective effect on muscle mass. MDPI 2018-11-16 /pmc/articles/PMC6262581/ /pubmed/30453501 http://dx.doi.org/10.3390/cells7110214 Text en © 2018 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 Article
Cécile, Polge
Julien, Aniort
Andrea, Armani
Agnès, Claustre
Cécile, Coudy-Gandilhon
Clara, Tournebize
Christiane, Deval
Lydie, Combaret
Daniel, Béchet
Marco, Sandri
Didier, Attaix
Daniel, Taillandier
UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment
title UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment
title_full UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment
title_fullStr UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment
title_full_unstemmed UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment
title_short UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment
title_sort ube2e1 is preferentially expressed in the cytoplasm of slow-twitch fibers and protects skeletal muscles from exacerbated atrophy upon dexamethasone treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262581/
https://www.ncbi.nlm.nih.gov/pubmed/30453501
http://dx.doi.org/10.3390/cells7110214
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