Evidence map›Paper›PMID 26968769›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016

Calcium-dependent phospholipase A2 modulates infection-induced diaphragm dysfunction.

Gerald S Supinski, Alexander P Alimov, Lin Wang, Xiao-Hong Song, Leigh A Callahan

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.3field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Mitoquinone mesylate (MitoQ) prevents sepsis-induced diaphragm dysfunction.Journal of applied physiology (Bethesda, Md. : 1985) · 2021
    Article
  5. Article
  6. MitoTEMPOL, a mitochondrial targeted antioxidant, prevents sepsis-induced diaphragm dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2020
    Article
  7. Article
  8. Review
  9. Review
  10. Taurine administration ablates sepsis induced diaphragm weakness.Respiratory physiology & neurobiology · 2020
    Article
  11. Review
  12. Article
  13. Ventilator-induced diaphragm dysfunction in critical illness.Experimental biology and medicine (Maywood, N.J.) · 2018
    Review
  14. Observational
  15. Review
  16. Article
  17. Observational
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 1 institution in 1 country.

Gerald S SupinskiDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky; and Center for Muscle Biology, University of Kentucky, Lexington, Kentucky.
Alexander P AlimovDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky; and Center for Muscle Biology, University of Kentucky, Lexington, Kentucky.
Lin WangDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky; and Center for Muscle Biology, University of Kentucky, Lexington, Kentucky.
Xiao-Hong SongDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky; and Center for Muscle Biology, University of Kentucky, Lexington, Kentucky.
Leigh A CallahanDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kentucky, Lexington, Kentucky; and Center for Muscle Biology, University of Kentucky, Lexington, Kentucky lacall2@email.uky.edu.
University of Kentucky · US

Funding

Treatment of Skeletal Muscle Dysfunction in ICU PatientsR01HL113494 · NHLBI · UNIVERSITY OF KENTUCKY · PI SUPINSKI, GERALD S. · 2013 to 2016
$2.3M
MAPK/PKR Modulation of Diaphragm WeaknessR01HL081525 · NHLBI · UNIVERSITY OF KENTUCKY · PI SUPINSKI, GERALD S. · 2006 to 2010
$1.8M
Effects of Sleep Deprivation on Infection Induced Organ FailureR01HL112085 · NHLBI · UNIVERSITY OF KENTUCKY · PI CALLAHAN, LEIGH A · 2013 to 2016
$1.5M
Caspase Mediated Diaphragmatic DysfunctionR01HL080429 · NHLBI · UNIVERSITY OF KENTUCKY · PI SUPINSKI, GERALD S. · 2006 to 2009
$1.4M
Respiratory Muscle WeaknessI01BX002132 · VA · VA MEDICAL CENTER - LEXINGTON, KY · PI SUPINSKI, GERALD S. · 2015 to 2018
–
BLRD VA I01 BX002132NHLBI NIH HHS R01 HL080429NHLBI NIH HHS R01 HL081525NHLBI NIH HHS R01 HL112085NHLBI NIH HHS R01 HL113494
6 · The paper itself

Abstract

Calpain activation contributes to the development of infection-induced diaphragm weakness, but the mechanisms by which infections activate calpain are poorly understood. We postulated that skeletal muscle calcium-dependent phospholipase A2 (cPLA2) is activated by cytokines and has downstream effects that induce calpain activation and muscle weakness. We determined whether cPLA2 activation mediates cytokine-induced calpain activation in isolated skeletal muscle (C2C12) cells and infection-induced diaphragm weakness in mice. C2C12 cells were treated with the following: 1) vehicle; 2) cytomix (TNF-α 20 ng/ml, IL-1β 50 U/ml, IFN-γ 100 U/ml, LPS 10 μg/ml); 3) cytomix + AACOCF3, a cPLA2 inhibitor (10 μM); or 4) AACOCF3 alone. At 24 h, we assessed cell cPLA2 activity, mitochondrial superoxide generation, calpain activity, and calpastatin activity. We also determined if SS31 (10 μg/ml), a mitochondrial superoxide scavenger, reduced cytomix-mediated calpain activation. Finally, we determined if CDIBA (10 μM), a cPLA2 inhibitor, reduced diaphragm dysfunction due to cecal ligation puncture in mice. Cytomix increased C2C12 cell cPLA2 activity (P < 0.001) and superoxide generation; AACOCF3 and SS31 blocked increases in superoxide generation (P < 0.001). Cytomix also activated calpain (P < 0.001) and inactivated calpastatin (P < 0.01); both AACOCF3 and SS31 prevented these changes. Cecal ligation puncture reduced diaphragm force in mice, and CDIBA prevented this reduction (P < 0.001). cPLA2 modulates cytokine-induced calpain activation in cells and infection-induced diaphragm weakness in animals. We speculate that therapies that inhibit cPLA2 may prevent diaphragm weakness in infected, critically ill patients.

Indexed as

AnimalsCell LineDiaphragmGroup IV Phospholipases A2MiceMuscle WeaknessSepsisSuperoxidesGroup IV Phospholipases A2SuperoxidescalpaincPLA2cytokinesdiaphragm weaknesssepsis

Identifiers

PMID26968769
PMCPMC4896095
OpenAlexW2294179546

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.