Evidence map›Paper›PMID 24206143›Full record

ArticleAntioxidants & redox signaling2014

Electrophilic fatty acid species inhibit 5-lipoxygenase and attenuate sepsis-induced pulmonary inflammation.

Khader Awwad, Svenja D Steinbrink, Timo Frömel, Nicole Lill, Johann Isaak, Ann-Kathrin Häfner, Jessica Roos, Bettina Hofmann, Heinrich Heide, Gerd Geisslinger and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 16% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Michael Acceptors as Anti-Cancer Compounds: Coincidence or Causality?International journal of molecular sciences · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Nitro Fatty Acids (NOMolecules (Basel, Switzerland) · 2021
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. 5-LOX inhibition by natural products.Nature chemical biology · 2020
    Article
  19. Review
  20. Review
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

14 authors at 2 institutions in 3 countries.

Khader Awwad1 Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University , Frankfurt am Main, Germany .
Svenja D Steinbrink
Timo Frömel
Nicole Lill
Johann Isaak
Ann-Kathrin Häfner
Jessica Roos
Bettina Hofmann
Heinrich Heide
Gerd Geisslinger
Dieter Steinhilber
Bruce A Freeman
Thorsten J Maier
Ingrid Fleming
Goethe University Frankfurt · DEUniversity of Pittsburgh · US

Funding

Vascular Subphenotypes of Lung DiseaseP01HL103455 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SHIVA, SRUTI · 2011 to 2020
$26.1M
Redox-Derived Pulmonary Anti-Inflammatory MediatorsR01HL064937 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 2000 to 2015
$5.6M
Redox Transduction of Nitric Oxide SignalingR37HL058115 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 2008 to 2017
$5.2M
Anti-Inflammatory Lipid Mediators in AsthmaR01HL132550 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN, HOLGUIN, FERNANDO · 2016 to 2019
$2.9M
NHLBI NIH HHS P01 HL103455NHLBI NIH HHS R01 HL064937NHLBI NIH HHS R01 HL132550NHLBI NIH HHS R37 HL058115
6 · The paper itself

Abstract

aimsThe reaction of nitric oxide and nitrite-derived species with polyunsaturated fatty acids yields electrophilic fatty acid nitroalkene derivatives (NO2-FA), which display anti-inflammatory properties. Given that the 5-lipoxygenase (5-LO, ALOX5) possesses critical nucleophilic amino acids, which are potentially sensitive to electrophilic modifications, we determined the consequences of NO2-FA on 5-LO activity in vitro and on 5-LO-mediated inflammation in vivo.

resultsStimulation of human polymorphonuclear leukocytes (PMNL) with nitro-oleic (NO2-OA) or nitro-linoleic acid (NO2-LA) (but not the parent lipids) resulted in the concentration-dependent and irreversible inhibition of 5-LO activity. Similar effects were observed in cell lysates and using the recombinant human protein, indicating a direct reaction with 5-LO. NO2-FAs did not affect the activity of the platelet-type 12-LO (ALOX12) or 15-LO-1 (ALOX15) in intact cells or the recombinant protein. The NO2-FA-induced inhibition of 5-LO was attributed to the alkylation of Cys418, and the exchange of Cys418 to serine rendered 5-LO insensitive to NO2-FA. In vivo, the systemic administration of NO2-OA to mice decreased neutrophil and monocyte mobilization in response to lipopolysaccharide (LPS), attenuated the formation of the 5-LO product 5-hydroxyeicosatetraenoic acid (5-HETE), and inhibited lung injury. The administration of NO2-OA to 5-LO knockout mice had no effect on LPS-induced neutrophil or monocyte mobilization as well as on lung injury. INNOVATION: Prophylactic administration of NO2-OA to septic mice inhibits inflammation and promotes its resolution by interfering in 5-LO-mediated inflammatory processes.

conclusionNO2-FAs directly and irreversibly inhibit 5-LO and attenuate downstream acute inflammatory responses.

Indexed as

AnimalsArachidonate 5-LipoxygenaseFatty Acids, UnsaturatedHumansLipoxygenase InhibitorsMiceNeutrophilsNitric OxidePneumoniaSepsisSignal TransductionArachidonate 5-LipoxygenaseFatty Acids, UnsaturatedLipoxygenase InhibitorsNitric Oxide

Identifiers

PMID24206143
PMCPMC4026401
OpenAlexW2086816976

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.