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Myofibrillar function differs markedly between denervated and dexamethasone-treated rat skeletal muscles: Role of mechanical load

Although there is good evidence to indicate a major role of intrinsic impairment of the contractile apparatus in muscle weakness seen in several pathophysiological conditions, the factors responsible for control of myofibrillar function are not fully understood. To investigate the role of mechanical...

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Autores principales: Yamada, Takashi, Ashida, Yuki, Tatebayashi, Daisuke, Himori, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785062/
https://www.ncbi.nlm.nih.gov/pubmed/31596883
http://dx.doi.org/10.1371/journal.pone.0223551
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author Yamada, Takashi
Ashida, Yuki
Tatebayashi, Daisuke
Himori, Koichi
author_facet Yamada, Takashi
Ashida, Yuki
Tatebayashi, Daisuke
Himori, Koichi
author_sort Yamada, Takashi
collection PubMed
description Although there is good evidence to indicate a major role of intrinsic impairment of the contractile apparatus in muscle weakness seen in several pathophysiological conditions, the factors responsible for control of myofibrillar function are not fully understood. To investigate the role of mechanical load in myofibrillar function, we compared the skinned fiber force between denervated (DEN) and dexamethasone-treated (DEX) rat skeletal muscles with or without neuromuscular electrical stimulation (ES) training. DEN and DEX were induced by cutting the sciatic nerve and daily injection of dexamethasone (5 mg/kg/day) for 7 days, respectively. For ES training, plantarflexor muscles were electrically stimulated to produce four sets of five isometric contractions each day. In situ maximum torque was markedly depressed in the DEN muscles compared to the DEX muscles (-74% vs. -10%), whereas there was not much difference in the degree of atrophy in gastrocnemius muscles between DEN and DEX groups (-24% vs. -17%). Similar results were obtained in the skinned fiber preparation, with a greater reduction in maximum Ca(2+)-activated force in the DEN than in the DEX group (-53% vs. -16%). Moreover, there was a parallel decline in myosin heavy chain (MyHC) and actin content per muscle volume in DEN muscles, but not in DEX muscles, which was associated with upregulation of NADPH oxidase (NOX) 2, neuronal nitric oxide synthase (nNOS), and endothelial NOS expression, translocation of nNOS from the membrane to the cytosol, and augmentation of mRNA levels of muscle RING finger protein 1 (MuRF-1) and atrogin-1. Importantly, mechanical load evoked by ES protects against DEN- and DEX-induced myofibrillar dysfunction and these molecular alterations. Our findings provide novel insights regarding the difference in intrinsic contractile properties between DEN and DEX and suggest an important role of mechanical load in preserving myofibrillar function in skeletal muscle.
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spelling pubmed-67850622019-10-19 Myofibrillar function differs markedly between denervated and dexamethasone-treated rat skeletal muscles: Role of mechanical load Yamada, Takashi Ashida, Yuki Tatebayashi, Daisuke Himori, Koichi PLoS One Research Article Although there is good evidence to indicate a major role of intrinsic impairment of the contractile apparatus in muscle weakness seen in several pathophysiological conditions, the factors responsible for control of myofibrillar function are not fully understood. To investigate the role of mechanical load in myofibrillar function, we compared the skinned fiber force between denervated (DEN) and dexamethasone-treated (DEX) rat skeletal muscles with or without neuromuscular electrical stimulation (ES) training. DEN and DEX were induced by cutting the sciatic nerve and daily injection of dexamethasone (5 mg/kg/day) for 7 days, respectively. For ES training, plantarflexor muscles were electrically stimulated to produce four sets of five isometric contractions each day. In situ maximum torque was markedly depressed in the DEN muscles compared to the DEX muscles (-74% vs. -10%), whereas there was not much difference in the degree of atrophy in gastrocnemius muscles between DEN and DEX groups (-24% vs. -17%). Similar results were obtained in the skinned fiber preparation, with a greater reduction in maximum Ca(2+)-activated force in the DEN than in the DEX group (-53% vs. -16%). Moreover, there was a parallel decline in myosin heavy chain (MyHC) and actin content per muscle volume in DEN muscles, but not in DEX muscles, which was associated with upregulation of NADPH oxidase (NOX) 2, neuronal nitric oxide synthase (nNOS), and endothelial NOS expression, translocation of nNOS from the membrane to the cytosol, and augmentation of mRNA levels of muscle RING finger protein 1 (MuRF-1) and atrogin-1. Importantly, mechanical load evoked by ES protects against DEN- and DEX-induced myofibrillar dysfunction and these molecular alterations. Our findings provide novel insights regarding the difference in intrinsic contractile properties between DEN and DEX and suggest an important role of mechanical load in preserving myofibrillar function in skeletal muscle. Public Library of Science 2019-10-09 /pmc/articles/PMC6785062/ /pubmed/31596883 http://dx.doi.org/10.1371/journal.pone.0223551 Text en © 2019 Yamada et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yamada, Takashi
Ashida, Yuki
Tatebayashi, Daisuke
Himori, Koichi
Myofibrillar function differs markedly between denervated and dexamethasone-treated rat skeletal muscles: Role of mechanical load
title Myofibrillar function differs markedly between denervated and dexamethasone-treated rat skeletal muscles: Role of mechanical load
title_full Myofibrillar function differs markedly between denervated and dexamethasone-treated rat skeletal muscles: Role of mechanical load
title_fullStr Myofibrillar function differs markedly between denervated and dexamethasone-treated rat skeletal muscles: Role of mechanical load
title_full_unstemmed Myofibrillar function differs markedly between denervated and dexamethasone-treated rat skeletal muscles: Role of mechanical load
title_short Myofibrillar function differs markedly between denervated and dexamethasone-treated rat skeletal muscles: Role of mechanical load
title_sort myofibrillar function differs markedly between denervated and dexamethasone-treated rat skeletal muscles: role of mechanical load
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785062/
https://www.ncbi.nlm.nih.gov/pubmed/31596883
http://dx.doi.org/10.1371/journal.pone.0223551
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