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Cited by 70Muscle Physiology and DisordersChronic Obstructive Pulmonary Disease (COPD) ResearchAmyotrophic Lateral Sclerosis Research

Involvement of the FoxO1/MuRF1/Atrogin-1 Signaling Pathway in the Oxidative Stress-Induced Atrophy of Cultured Chronic Obstructive Pulmonary Disease Myotubes

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Pomiès, Pascal, Blaquière, Marine, Maury, Jonathan, Mercier, Jacques, Gouzi, Fares, Hayot, Maurice·2016·PLOS ONE
DOI 10.1371/journal.pone.0160092PMC PMC4987766
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Abstract

Oxidative stress is thought to be one of the most important mechanisms implicated in the muscle wasting of chronic obstructive pulmonary disease (COPD) patients, but its role has never been demonstrated. We therefore assessed the effects of both pro-oxidant and antioxidant treatments on the oxidative stress levels and atrophic signaling pathway of cultured COPD myotubes. Treatment of cultured COPD myotubes with the pro-oxidant molecule H2O2 resulted in increased ROS production (P = 0.002) and protein carbonylation (P = 0.050), in association with a more pronounced atrophy of the myotubes, as reflected by a reduced diameter (P = 0.003), and the activated expression of atrophic markers MuRF1 and FoxO1 (P = 0.022 and P = 0.030, respectively). Conversely, the antioxidant molecule ascorbic acid induced a reduction in ROS production (P<0.001) and protein carbonylation (P = 0.019), and an increase in the myotube diameter (P<0.001) to a level similar to the diameter of healthy subject myotubes, in association with decreased expression levels of MuRF1, atrogin-1 and FoxO1 (P<0.001, P = 0.002 and P = 0.042, respectively). A significant negative correlation was observed between the variations in myotube diameter and the variations in the expression of MuRF1 after antioxidant treatment (P = 0.047). Moreover, ascorbic acid was able to prevent the H2O2-induced atrophy of COPD myotubes. Last, the proteasome inhibitor MG132 restored the basal atrophy level of the COPD myotubes and also suppressed the H2O2-induced myotube atrophy. These findings demonstrate for the first time the involvement of oxidative stress in the atrophy of COPD peripheral muscle cells in vitro, via the FoxO1/MuRF1/atrogin-1 signaling pathway of the ubiquitin/proteasome system.

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  • Several studies point towards a direct relationship between oxidative stress, atrophy, and the ubiquitin-proteasome pathway, including data from experimental models.

    “However, several studies point towards a direct relationship between oxidative stress, atrophy, and the ubiquitin–proteasome pathway [131], including data obtained in experimental models [132].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [131]

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Cited by

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Authors
Pomiès, P., Blaquière, M., Maury, J., Mercier, J., Gouzi, F., & Hayot, M.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Pomiès, Pascal
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2016-08-15
Volume
11
Issue
8
Pages
e0160092
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0160092
PMC
PMC4987766
OpenAlex
W2513165392
Cited by
70
References
1
Citations by year
2026: 7 · 2025: 7 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 12 · 2019: 3 · 2018: 7 · 2017: 2 · 2016: 1
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Association Nationale de la Recherche et de la Technologie
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
chronic obstructive pulmonary disease, muscle atrophy, oxidative stress, FOXO1, MuRF1, atrogin-1, ubiquitin-proteasome system, myotubes, hydrogen peroxide, vitamin C, reactive oxygen species, protein carbonylation, proteasome inhibition, MG132, skeletal muscle atrophy
MeSH terms
Tripartite Motif Proteins, Forkhead Box Protein O1, Aged, Antioxidants, Ascorbic Acid, Female, Humans, Hydrogen Peroxide, Leupeptins, Male, Middle Aged, Muscle Proteins, Muscular Atrophy, Signal Transduction, Oxidative Stress, Muscle Fibers, Skeletal, Pulmonary Disease, Chronic Obstructive, Ubiquitin-Protein Ligases, SKP Cullin F-Box Protein Ligases

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