ArticleAmerican journal of respiratory and critical care medicine2006
Activation of the ubiquitin-proteasome pathway in the diaphragm in chronic obstructive pulmonary disease.
Article in American journal of respiratory and critical care medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 124 citations in OpenAlex.
- Inspiratory Muscle Training plus Pulmonary Rehabilitation versus Rehabilitation alone in COPD A Systematic Review of Randomized Controlled Trials.F1000Research · 2026Pooled it
- Evaluation of common protein biomarkers involved in the pathogenesis of respiratory diseases with proteomic methods: A systematic review.Immunity, inflammation and disease · 2023Pooled it
- Cycle ergometer and inspiratory muscle training offer modest benefit compared with cycle ergometer alone: a comprehensive assessment in stable COPD patients.International journal of chronic obstructive pulmonary disease · 2017Trial
- The associations of human genetic variations with airway microbiome, environmental exposures, and respiratory health.mSystems · 2026Article
- MTMR14 depletion aggravates intrapulmonary inflammation and emphysema in experimental COPD through activating macrophage M1 polarization.Respiratory research · 2025Article
- Mechanisms and markers of lung ageing in health and disease.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Identification and Experimental Validation of Biomarkers Related to MiR-125a-5p in Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2025Article
- Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters.Nature aging · 2023Article
- Atrophy signaling pathways in respiratory and limb muscles of guinea pigs exposed to chronic cigarette smoke: role of soluble guanylate cyclase stimulation.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Article
- The myokine Fibcd1 is an endogenous determinant of myofiber size and mitigates cancer-induced myofiber atrophy.Nature communications · 2022Article
- Comparison of Ultrasound Measurements for Diaphragmatic Mobility, Diaphragmatic Thickness, and Diaphragm Thickening Fraction with Each Other and with Lung Function in Patients with Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2022Observational
- Nox4 Knockout Does Not Prevent Diaphragm Atrophy, Contractile Dysfunction, or Mitochondrial Maladaptation in the Early Phase Post-Myocardial Infarction in Mice.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Article
- Nutritional Status and Body Composition in Patients Suffering From Chronic Respiratory Diseases and Its Correlation With Pulmonary Rehabilitation.Frontiers in rehabilitation sciences · 2021Review
- Effect of Oxidative Stress on Diaphragm Dysfunction and Exercise Intervention in Chronic Obstructive Pulmonary Disease.Frontiers in physiology · 2021Review
- Proteasome Biology: Chemistry and Bioengineering Insights.Polymers · 2020Review
- Diaphragm contractile weakness due to reduced mechanical loading: role of titin.American journal of physiology. Cell physiology · 2019Review
- Correlation between diaphragm thickness and respiratory synergist muscle activity according to severity of chronic obstructive pulmonary disease.Journal of physical therapy science · 2018Article
- Impaired calcium signaling in muscle fibers from intercostal and foot skeletal muscle in a cigarette smoke-induced mouse model of COPD.Muscle & nerve · 2017Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
rationaleStudies show that the myosin content of the diaphragm in patients with mild to moderate chronic obstructive pulmonary disease (COPD) is reduced, compromising diaphragm contractile performance. The mechanisms for reduced contractile protein content are unknown. In the present study we hypothesized that the loss of contractile protein content is associated with activation of the ubiquitin-proteasome pathway in the diaphragm of patients with mild to moderate COPD.
methodsProteolytic activity of isolated 20S proteasomes was determined in diaphragm biopsies from patients with and without COPD (predicted mean FEV1, 66 and 93%, respectively). In addition, we determined 20S proteasome subunit C8 protein levels by means of Western blotting, ubiquitin-ligase mRNA levels by means of real-time polymerase chain reaction, and caspase-3 activity by determining the hydrolysis of fluorogenic substrates.
resultsThe 20S proteasome activity was about threefold increased in the diaphragm of patients with COPD. C8 protein levels were not significantly different between COPD and non-COPD diaphragm, indicating increased specific activity of individual proteasomes, rather than an increased number of proteasomes. mRNA levels of the muscle-specific ubiquitin-ligase MAFbx were significantly higher in diaphragm from patients with COPD compared with patients without COPD. Caspase-3-mediated cleavage of actomyosin complexes is considered an initial step in muscle wasting, yielding fragments that can be degraded by the ubiquitin-proteasome pathway. In line with the increased ubiquitin-proteasome activity, caspase-3 activity was higher in diaphragm homogenates from patients with COPD.
conclusionsThe present study is the first to demonstrate increased activity of the ubiquitin-proteasome pathway in COPD diaphragm. Importantly, these changes occur in patients with only mild to moderate COPD (Global Initiative for Chronic Obstructive Lung Disease stage I/II).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.