Evidence map›Paper›PMID 24681580›Full record

ArticleAnesthesiology2014

Inhibition of the ubiquitin-proteasome pathway does not protect against ventilator-induced accelerated proteolysis or atrophy in the diaphragm.

Ashley J Smuder, W Bradley Nelson, Matthew B Hudson, Andreas N Kavazis, Scott K Powers

Open access · greenAbstract read
In one paragraph

Article in Anesthesiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

27 citing papers in PubMed, 38 citations in OpenAlex.

  1. Ventilator-induced diaphragmatic dysfunction: pathophysiology, monitoring and advances in potential treatment and prevention.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
  2. Diaphragm Function in Health and Disease.Advances in experimental medicine and biology · 2025
    Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Emerging Strategies Targeting Catabolic Muscle Stress Relief.International journal of molecular sciences · 2020
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. [Diaphragm dysfunction : Facts for clinicians].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2018
    Review
  17. The Renin-Angiotensin System and Skeletal Muscle.Exercise and sport sciences reviews · 2018
    Review
  18. Article
  19. Article
  20. The role of calpains in ventilator-induced diaphragm atrophy.Intensive care medicine experimental · 2017
    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

5 authors at 3 institutions in 1 country.

Ashley J SmuderFrom the Department of Applied Physiology and Kinesiology, Center for Exercise Science, University of Florida, Gainesville, Florida (A.J.S., S.K.P.); Division of Mathematics, Computer, and Natural Sciences, Department of Natural Sciences, Ohio Dominican University, Columbus, Ohio (W.B.N.); Department of Medicine, Emory University, Atlanta, Georgia (M.B.H.); and School of Kinesiology, Auburn University, Auburn, Alabama (A.N.K.).
W Bradley Nelson
Matthew B Hudson
Andreas N Kavazis
Scott K Powers
Ohio Dominican University · USEmory University · USUniversity of Florida · US

Funding

Mechanical Ventilation, Oxidative Stress, and Diaphragmatic AtrophyR01HL087839 · NHLBI · UNIVERSITY OF FLORIDA · PI POWERS, SCOTT K. · 2009 to 2012
$1.4M
NHLBI NIH HHS R01 HL087839NHLBI NIH HHS R01 HL780839
6 · The paper itself

Abstract

backgroundMechanical ventilation (MV) is a life-saving intervention in patients with acute respiratory failure. However, prolonged MV results in ventilator-induced diaphragm dysfunction (VIDD), a condition characterized by both diaphragm fiber atrophy and contractile dysfunction. Previous work has shown that calpain, caspase-3, and the ubiquitin-proteasome pathway (UPP) are all activated in the diaphragm during prolonged MV. However, although it is established that both calpain and caspase-3 are important contributors to VIDD, the role that the UPP plays in the development of VIDD remains unknown. These experiments tested the hypothesis that inhibition of the UPP will protect the diaphragm against VIDD.

methodsThe authors tested this prediction in an established animal model of MV using a highly specific UPP inhibitor, epoxomicin, to prevent MV-induced activation of the proteasome in the diaphragm (n = 8 per group).

resultsThe results of this study reveal that inhibition of the UPP did not prevent ventilator-induced diaphragm muscle fiber atrophy and contractile dysfunction during 12 h of MV. Also, inhibition of the UPP does not affect MV-induced increases in calpain and caspase-3 activity in the diaphragm. Finally, administration of the proteasome inhibitor did not protect against the MV-induced increases in the expression of the E3 ligases, muscle ring finger-1 (MuRF1), and atrogin-1/MaFbx.

conclusionCollectively, these results indicate that proteasome activation does not play a required role in VIDD development during the first 12 h of MV.

Indexed as

AnesthesiaAnimalsAntibiotics, AntineoplasticAtrophyBlotting, WesternBoronic AcidsBortezomibCaspase 3DiaphragmDNA, ComplementaryFemaleMuscle ContractionMuscle ProteinsOligopeptidesProtease InhibitorsProteasome Endopeptidase ComplexAntibiotics, AntineoplasticBoronic AcidsBortezomibCaspase 3DNA, ComplementaryepoxomicinFbxo32 protein, ratMuscle ProteinsOligopeptidesProtease InhibitorsProteasome Endopeptidase ComplexPyrazinesSKP Cullin F-Box Protein LigasesTrim63 protein, ratTripartite Motif ProteinsUbiquitinUbiquitin-Protein Ligases

Identifiers

PMID24681580
PMCPMC4096949
OpenAlexW2060721226

What OpenQuestion holds

Textmetadata
LicenceTDM
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.