Evidence map›Paper›PMID 16917114›Full record

ArticleAmerican journal of respiratory and critical care medicine2006

Activation of the ubiquitin-proteasome pathway in the diaphragm in chronic obstructive pulmonary disease.

Coen A C Ottenheijm, Leo M A Heunks, Yi-Ping Li, Bingwen Jin, Ronnie Minnaard, Hieronymus W H van Hees, P N Richard Dekhuijzen

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 2 pooled it
3.7field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 124 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Article
  6. Mechanisms and markers of lung ageing in health and disease.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Observational
  13. 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 · 2021
    Article
  14. Review
  15. Review
  16. Review
  17. Diaphragm contractile weakness due to reduced mechanical loading: role of titin.American journal of physiology. Cell physiology · 2019
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 2 countries.

Coen A C OttenheijmDepartment of Pulmonary Diseases, 454, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands. c.ottenheijm@long.umcn.nl
Leo M A Heunks
Yi-Ping Li
Bingwen Jin
Ronnie Minnaard
Hieronymus W H van Hees
P N Richard Dekhuijzen
Radboud University Nijmegen · NL

Funding

Regulation of Skeletal Muscle RegenerationR01AR049022 · NIAMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LI, YI-PING · 2003 to 2012
$3.0M
NIAMS NIH HHS AR049022NIAMS NIH HHS R01 AR049022
6 · The paper itself

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).

Indexed as

AgedCaspase 3DiaphragmFemaleHumansImmunohistochemistryMaleMiddle AgedMuscle ContractionMuscle ProteinsMyosinsProteasome Endopeptidase ComplexPulmonary Disease, Chronic ObstructiveSKP Cullin F-Box Protein LigasesTripartite Motif ProteinsUbiquitinCaspase 3FBXO32 protein, humanMuscle ProteinsMyosinsProteasome Endopeptidase ComplexSKP Cullin F-Box Protein LigasesTRIM63 protein, humanTripartite Motif ProteinsUbiquitinUbiquitin-Protein Ligases

Identifiers

PMID16917114
PMCPMC2648103
OpenAlexW2149763158

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.