Autophagy in Locomotor Muscles of Patients with Chronic Obstructive Pulmonary Disease
Open accessAbstract
RATIONALE: Locomotor muscle atrophy develops in patients with chronic obstructive pulmonary disease (COPD) partly because of increased protein degradation by the ubiquitin-proteasome system. It is not known if autophagy also contributes to protein degradation. OBJECTIVES: To investigate whether autophagy is enhanced in locomotor muscles of stable patients with COPD, to quantify autophagy-related gene expression in these muscles, and to identify mechanisms of autophagy induction. METHODS: Muscle biopsies were obtained from two cohorts of control subjects and patients with COPD and the numbers of autophagosomes in the vastus lateralis and tibialis anterior muscles, the levels of LC3B protein lipidation, and the expression of autophagy-related genes were measured in the vastus lateralis muscle. To investigate potential pathways that might induce the activation of autophagy, measures were taken of protein kinase B (AKT), mTORC1, and AMPK pathway activation, transcription factor regulation, proteasome activation, and oxidative stress. MEASUREMENTS AND MAIN RESULTS: Autophagy is enhanced in the locomotor muscles of patients with COPD as shown by significantly higher numbers of autophagosomes in affected muscles as compared with control subjects. Autophagosome number inversely correlates with FEV1. In the vastus lateralis, LC3B protein lipidation is increased by COPD and the expression of autophagy-related gene expressions is up-regulated. LC3B lipidation inversely correlates with thigh cross-sectional area, FEV1, and FEV1/FVC ratio. Enhanced autophagy is associated with activation of the AMPK pathway and FOXO transcription factors, inhibition of the mTORC1 and AKT pathways, and the development of oxidative stress. CONCLUSIONS: Autophagy is significantly enhanced in locomotor muscles of stable patients with COPD. The degree of autophagy correlates with severity of muscle atrophy and lung function impairment.
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A significant number of studies reported an increased LC3BII/LC3BI ratio and/or LC3B lipidation in COPD quadriceps.
“A significant number of studies reported an increased LC3BII/LC3BI ratio and/or LC3B lipidation (another marker of activation) in COPD quadriceps [123,182,183].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [182]
Searches for the LC3BII/LC3BI ratio, LC3B lipidation, and quadriceps findings returned no relevant full-text passage. The only matching statement was labeled Abstract, which is not admissible evidence under the stated rubric. (LLM, conf=0.65)
Experimental — accuracy not yet measuredTwo studies reported increased ultrastructural autophagosome counts in the quadriceps and/or tibialis anterior of COPD patients.
“Furthermore, two studies reported increased ultrastructural autophagosome counts, respectively, in the quadriceps [123] and both in the quadriceps and tibialis anterior [182].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [182]
The indexed search returned the paper’s Abstract (no page given) and bibliographic metadata, but no full-text Methods or Results passage. The abstract cannot serve as evidence under the specified rubric, so the claim about ultrastructural autophagosome counts in the quadriceps and tibialis anterior remains unverifiable from the available passages. Searches included “autophagosome,” “electron microscopy,” and “vastus lateralis.” (LLM, conf=0.72)
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Cites
Bodine, S. C., Stitt, T. N., Gonzalez, M., Kline, W. O., Stover, G. L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J. C., Glass, D. J., et al. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1014 · Cited by 2,752 · see citing works
Autophagy is required to maintain muscle mass.
Masiero, E., Agatea, L., Mammucari, C., Blaauw, B., Loro, E., Komatsu, M., Metzger, D., Reggiani, C., Schiaffino, S., & Sandri, M. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.10.008 · Cited by 1,282 · see citing works
Self-citationRegulation of autophagy by ROS: physiology and pathology
Scherz-Shouval, R., & Elazar, Z. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.007 · Cited by 1,263 · see citing works
PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase
Sancak, Y., Thoreen, C. C., Peterson, T. R., Lindquist, R. A., Kang, S. A., Spooner, E., Carr, S. A., & Sabatini, D. M. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.003 · Cited by 1,236 · see citing works
Ribosomal S6 Kinase Signaling and the Control of Translation
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Mitochondrial Dysfunction in Skeletal Muscle Pathologies
Abrigo, J., Simon, F., Cabrera, D., Vilos, C., & Cabello-Verrugio, C. (2019) · Current Protein & Peptide Science · doi:10.2174/1389203720666190402100902 · Cited by 88 · see citing works
Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting
Henrot, P., Dupin, I., Schilfarth, P., Esteves, P., Blervaque, L., Zysman, M., Gouzi, F., Hayot, M., Pomiès, P., & Berger, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076454 · Cited by 85 · see citing works
“A significant number of studies reported an increased LC3BII/LC3BI ratio and/or LC3B lipidation (another marker of activation) in COPD quadriceps [123,182,183].”
BackgroundAutophagy in Pulmonary Diseases
Nakahira, K., Pabon Porras, M. A., & Choi, A. M. K. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201512-2468so · Cited by 78 · see citing works
Vignaud, J., Loiseau, C., Hérault, J., Mayer, C., Côme, M., Martin, I., & Ulmann, L. (2023) · Antioxidants · doi:10.3390/antiox12051050 · Cited by 72 · see citing works
Byrne, C. A., McNeil, A. T., Koh, T. J., Brunskill, A. F., & Fantuzzi, G. (2019) · PLOS ONE · doi:10.1371/journal.pone.0222345 · Cited by 15 · see citing works
- Authors
- Guo, Y., Gosker, H. R., Schols, A. M. W. J., Kapchinsky, S., Bourbeau, J., Sandri, M., Jagoe, R. T., Debigaré, R., Maltais, F., Taivassalo, T., & Hussain, S. N. A.
- Affiliations
- Department of Critical Care and
- Maastricht University Medical Centre (NL)
- Department of Kinesiology, and
- McGill University Health Centre (CA)
- Veneto Institute of Molecular Medicine (IT)
- Jewish General Hospital (CA)
- Institut universitaire de cardiologie et de pneumologie de Québec (CA)
- Corresponding author
- Hussain, Sabah N. A.
- ORCID
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-12-01
- Volume
- 188
- Issue
- 11
- Pages
- 1313-1320
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2169536980
- Cited by
- 117
- References
- 6
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 5 · 2022: 15 · 2021: 4 · 2020: 11 · 2019: 10 · 2018: 9 · 2017: 13 · 2016: 18 · 2015: 7 · 2014: 8
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Padua Research Archive (University of Padova) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Helsingin Yliopisto
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- autophagy, chronic obstructive pulmonary disease, ubiquitin-proteasome system, protein degradation, LC3B lipidation, autophagosomes, AMPK signaling, mTORC1, AKT pathway, FOXO transcription factors, oxidative stress, vastus lateralis, tibialis anterior, FEV1, muscle cross-sectional area
- MeSH terms
- Aged, Autophagy, Biopsy, Female, Humans, Locomotion, Male, Middle Aged, Muscular Atrophy, Oxidative Stress, Muscle, Skeletal, Pulmonary Disease, Chronic Obstructive, Quadriceps Muscle, Proteolysis
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