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Cited by 148Muscle Physiology and DisordersChronic Obstructive Pulmonary Disease (COPD) ResearchNutrition and Health in Aging

Does Oxidative Stress Modulate Limb Muscle Atrophy in Severe COPD Patients?

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Fermoselle, Clara, Rabinovich, Roberto, Ausín, Pilar, Puig-Vilanova, Ester, Coronell, Carlos, Sanchez, Francisco, Roca, Josep, Gea, Joaquim +1 more·2012·European Respiratory Journal
DOI 10.1183/09031936.00137211
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Abstract

Oxidative stress may differentially regulate protein loss within peripheral muscles of severe chronic obstructive pulmonary disease (COPD) patients exhibiting different body composition. Oxidation levels of proteins, myosin heavy chain (MyHC) and myonuclei, superoxide anion, antioxidants, actin, creatine kinase, carbonic anhydrase-3, ubiquitin–proteasome system, redox-signalling pathways, inflammation and muscle structure, and damage were quantified in limb muscles of severe COPD patients with and without muscle wasting, and in sedentary controls. Compared with controls, in the quadriceps of muscle-wasted COPD patients, levels of protein carbonylation, oxidation of MyHC and myonuclei, superoxide anion production, superoxide dismutase, total protein ubiquinitation, E2 14k, atrogin-1, FoxO1 and p65 were higher, while content of MyHC, creatine kinase, carbonic anhydrase-3, myogenin, and fast-twitch fibre size were decreased. Importantly, in nonwasted COPD patients, where MyHC was more oxidised than in controls, its content was preserved. Muscle inflammation and glutathione levels did not differ between patients and controls. In all patients, muscle structure abnormalities were increased, while muscle force and exercise capacity were reduced. In severe COPD, while muscle oxidative stress increases regardless of their body composition, protein ubiquitination and loss of MyHC were enhanced only in patients exhibiting muscle atrophy. Oxidative stress does not seem to directly modulate muscle protein loss in these patients.

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  • Direct evidence of increased oxidative stress includes increased nuclear and mitochondrial superoxide anions in the quadriceps of sarcopenic COPD patients compared to nonsarcopenic patients.

    “Direct evidence includes increased nuclear and mitochondrial superoxide anions in the quadriceps of sarcopenic COPD patients compared to nonsarcopenic patients [118].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [118]

    The Nuclear superoxide anion detection section and Figure 1 caption report higher nuclear superoxide staining in both wasted and nonwasted COPD patients than in healthy controls. The Superoxide anion in muscle compartments section and Figure 2 caption report higher mitochondrial superoxide only in wasted patients relative to healthy controls. Neither reports the claimed increase in nuclear and mitochondrial superoxide in wasted patients compared directly with nonwasted patients. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Increased Mn-superoxide dismutase (SOD) and Cu-Zn-SOD protein levels have been demonstrated in COPD quadriceps, whereas unchanged SOD content and decreased SOD activity have been reported in another study, and unchanged MnSOD, Cu/ZnSOD, and catalase expressions have been found in cultured COPD myoblasts and myotubes.

    “For example, increased Mn-superoxide dismutase (SOD) and Cu-Zn-SOD protein levels have been demonstrated in the quadriceps [118,127], whereas unchanged SOD content and decreased SOD activity have been reported in another study [122], and unchanged MnSOD, Cu/ZnSOD, and catalase expressions in cultured COPD myoblasts and myotubes have been found [128].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [118]

    Split into 3 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable, 2 not checked. Expand the claim to see per-atom verdicts.

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  • Multiple studies point towards increased protein carbonylation in COPD quadriceps compared to healthy controls, including total protein content and specific proteins such as glycolytic enzymes, antioxidant enzymes, and myosin heavy chain.

    “Multiple studies point towards an increased protein carbonylation in COPD quadriceps compared to healthy controls, including total protein content but also specific proteins such as glycolytic enzymes (creatine kinase), antioxidant enzymes (glutathione peroxidase), and myosin heavy chain [118,120,121,122].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [118]

    The Protein carbonylation and Contractile and functional muscle proteins sections report higher total protein carbonylation and carbonylated myosin heavy chain in COPD limb muscle than in controls. The paper reports reduced creatine kinase content and unchanged glutathione peroxidase content, but does not establish increased carbonylation of either enzyme. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In COPD, increased proteolysis is mainly mediated by overactivation of the ubiquitin (26S)-proteasome system, activated via the muscle-specific E3-ubiquitin ligases Atrogin-1/MAFbx and TRIM63/MuRF-1, which are increased in COPD quadriceps.

    “In COPD, increased proteolysis is mainly mediated by an overactivation of the ubiquitin (26S)–proteasome system, activated via the muscle-specific E3-ubiquitin ligases Atrogin-1/MAFbx and TRIM63/MuRF-1, also named atrogenes, which are increased in COPD quadriceps [118,165].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [118]

    The Ubiquitin-proteasome system section reports greater protein ubiquitination and atrogin-1 in the vastus lateralis of muscle-wasted COPD patients, supporting part of the claim. It explicitly reports that MuRF-1 did not differ between study groups; the discussion describes the system's role in severe COPD muscle atrophy as likely rather than establishing that increased proteolysis is mainly mediated by its overactivation. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Unchanged glutathione and catalase quadriceps levels have been reported in COPD.

    “Unchanged glutathione and catalase quadriceps levels have been reported [118,122].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [118]

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Authors
Fermoselle, C., Rabinovich, R., Ausín, P., Puig-Vilanova, E., Coronell, C., Sanchez, F., Roca, J., Gea, J., & Barreiro, E.
Affiliations
  • Universitat Pompeu Fabra (ES)
  • Instituto de Salud Carlos III (ES)
ORCID
Venue
European Respiratory Journal
Publisher
European Respiratory Society (ERS)
Published
2012-03-09
Volume
40
Issue
4
Pages
851-862
ISSN
  • 0903-1936 (ISSN-L)
  • 1399-3003
DOI
10.1183/09031936.00137211
OpenAlex
W2098653166
Cited by
148
References
3
Citations by year
2026: 4 · 2025: 1 · 2024: 5 · 2023: 5 · 2022: 15 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 14 · 2017: 14 · 2016: 20 · 2015: 19 · 2014: 19 · 2013: 14 · 2012: 6
FWCI
7.44
Type
journal article
Language
en
Open access
Locations
  • European Respiratory Journal (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Universitat Pompeu Fabra
  • Instituto de Salud Carlos III
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 › Physiology › Nutrition and Health in Aging
Keywords
chronic obstructive pulmonary disease, muscle atrophy, oxidative stress, protein carbonylation, ubiquitination, ubiquitin-proteasome system, atrogin-1, FOXO1, superoxide, muscle inflammation, muscle fiber size, quadriceps, body composition, exercise capacity
MeSH terms
Aged, Extremities, Humans, Inflammation, Male, Middle Aged, Muscle Proteins, Muscular Atrophy, Oxidation-Reduction, Case-Control Studies, Oxidative Stress, Muscle, Skeletal, Pulmonary Disease, Chronic Obstructive, Quadriceps Muscle

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