MuRF-1 and Atrogin-1 Protein Expression and Quadriceps Fiber Size and Muscle Mass in Stable Patients with COPD
Open accessAbstract
INTRODUCTION: Animal studies demonstrate the importance of the E3 ubiquitin ligases, Muscle RING-Finger Protein 1 (MuRF-1) and atrogin-1, in muscle protein degradation during acute muscle atrophy. Small clinical studies suggest MuRF-1 and atrogin-1 expression in the quadriceps muscle is also increased in stable patients with Chronic Obstructive Pulmonary Disease compared to controls. However, it remains unclear whether these ligases have a role in maintaining a muscle-wasted state in COPD patients. METHODS: 32 stable COPD patients (16 with a low fat-free mass index (FFMI), 16 with a normal FFMI) and 15 controls underwent lung function and quadriceps strength tests and a percutaneous quadriceps biopsy. Quadriceps MuRF-1 and atrogin-1 protein were quantified with western blotting. Quadriceps fiber cross-sectional area (CSA) and fiber proportions were determined by immunohistochemistry on muscle sections. MuRF-1 and atrogin-1 levels were compared between COPD patients with and without a low FFMI, and between patients and controls, and correlations between MuRF-1 and atrogin-1 levels and quadriceps fiber CSA in the patients were investigated. RESULTS: Atrogin-1 protein levels were lower in patients than controls, but similar in patients with a low and normal FFMI. MuRF-1 levels did not differ between any groups. MuRF-1 and atrogin-1 levels were not associated with quadriceps fiber CSA or quadriceps strength in patients. CONCLUSIONS: Chronic upregulation of ubiquitin ligases was not evident in the quadriceps muscle of stable COPD patients with a low muscle mass. This does not exclude the possibility of transient increases in ubiquitin ligases during acute catabolic episodes.
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Some studies have failed to report a significant difference in atrogenes between COPD patients and healthy subjects, possibly due to timing of assessment.
“Of note, some studies have failed to report a significant difference between COPD patients and healthy subjects [166], possibly due to the timing of the assessment.”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [166]
The Results report no significant difference in MuRF-1 protein between COPD patients and controls, but atrogin-1 protein was significantly lower in the COPD group. The Discussion considers measurement timing as a possible reason ubiquitin-ligase levels may not be elevated in stable patients; it does not establish timing as the cause of the MuRF-1 result. Thus the claim is supported for MuRF-1, not for both atrogenes. (LLM, conf=0.89)
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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
“Of note, some studies have failed to report a significant difference between COPD patients and healthy subjects [166], possibly due to the timing of the assessment.”
Result
- Authors
- Natanek, S. A., Riddoch-Contreras, J., Marsh, G. S., Hopkinson, N. S., Moxham, J., Man, W. D.-C., Kemp, P. R., & Polkey, M. I.
- Affiliations
- Royal Brompton & Harefield NHS Foundation Trust (GB)
- Imperial College London (GB)
- Corresponding author
- Polkey, Michael I.
- Venue
- COPD: Journal of Chronic Obstructive Pulmonary Disease
- Publisher
- Informa UK Limited
- Published
- 2013-07-11
- Volume
- 10
- Issue
- 5
- Pages
- 618-624
- ISSN
- 1541-2555 (ISSN-L)
- 1541-2563
- PMC
- PMC4002632
- OpenAlex
- W2167664180
- Cited by
- 32
- References
- 4
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 4
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- COPD Journal of Chronic Obstructive Pulmonary Disease (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- National Institute for Health and Care Research (DHCS/07/07/009, CTF-01-12-04)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- MuRF1, atrogin-1, E3 ubiquitin ligase, chronic obstructive pulmonary disease, muscle atrophy, muscle protein degradation, quadriceps, muscle fiber cross-sectional area, fat-free mass index, muscle mass, muscle strength
- MeSH terms
- Tripartite Motif Proteins, Aged, Female, Humans, Male, Middle Aged, Muscle Proteins, Muscular Atrophy, Organ Size, Severity of Illness Index, Case-Control Studies, Muscle Fibers, Skeletal, Pulmonary Disease, Chronic Obstructive, Ubiquitin-Protein Ligases, SKP Cullin F-Box Protein Ligases, Quadriceps Muscle
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