Evidence map›Paper›PMID 24559999›Full record

ArticleBiophysical journal2014

Modeling of eicosanoid fluxes reveals functional coupling between cyclooxygenases and terminal synthases.

Yasuyuki Kihara, Shakti Gupta, Mano R Maurya, Aaron Armando, Ishita Shah, Oswald Quehenberger, Christopher K Glass, Edward A Dennis, Shankar Subramaniam

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 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

23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.

  1. The Anti-Metastatic Role of Aspirin in Cancer: A Systematic Review.International journal of molecular sciences · 2026
    Pooled it
  2. Pooled it
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  4. An adaptableMolecular omics · 2024
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  6. From transcriptomics to digital twins of organ function.Frontiers in cell and developmental biology · 2024
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  7. Article
  8. Redox Imbalance and Its Metabolic Consequences in Tick-Borne Diseases.Frontiers in cellular and infection microbiology · 2022
    Review
  9. Article
  10. Review
  11. Phospholipase ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019
    Review
  12. Article
  13. Article
  14. Review
  15. IL-4 up-regulates cyclooxygenase-1 expression in macrophages.The Journal of biological chemistry · 2017
    Article
  16. Review
  17. Article
  18. Review
  19. Contribution of alveolar type II cell-derived cyclooxygenase-2 to basal airway function, lung inflammation, and lung fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016
    Article
  20. Eicosanoid storm in infection and inflammation.Nature reviews. Immunology · 2015
    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

9 authors at 1 institution in 1 country.

Yasuyuki KiharaDepartment of Chemistry and Biochemistry and Pharmacology, School of Medicine, University of California at San Diego, La Jolla, California; Department of Bioengineering, University of California at San Diego, La Jolla, California.
Shakti GuptaDepartment of Bioengineering, University of California at San Diego, La Jolla, California.
Mano R MauryaDepartment of Bioengineering, University of California at San Diego, La Jolla, California.
Aaron ArmandoDepartment of Chemistry and Biochemistry and Pharmacology, School of Medicine, University of California at San Diego, La Jolla, California.
Ishita ShahDepartment of Chemistry and Biochemistry and Pharmacology, School of Medicine, University of California at San Diego, La Jolla, California.
Oswald QuehenbergerDepartment of Chemistry and Biochemistry and Pharmacology, School of Medicine, University of California at San Diego, La Jolla, California; Department of Medicine, School of Medicine, University of California at San Diego, La Jolla, California.
Christopher K GlassDepartment of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California.
Edward A DennisDepartment of Chemistry and Biochemistry and Pharmacology, School of Medicine, University of California at San Diego, La Jolla, California. Electronic address: edennis@ucsd.edu.
Shankar SubramaniamDepartment of Chemistry and Biochemistry and Pharmacology, School of Medicine, University of California at San Diego, La Jolla, California; Department of Bioengineering, University of California at San Diego, La Jolla, California; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California. Electronic address: shankar@ucsd.edu.
University of California San Diego · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
STEROL LIPIDSU54GM069338 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DENNIS, EDWARD A · 2003 to 2013
$72.2M
NCI NIH HHS P30 CA023100NIGMS NIH HHS U54 GM069338
6 · The paper itself

Abstract

Eicosanoids, including prostaglandins (PG) and leukotrienes, are lipid mediators derived from arachidonic acid. A quantitative and biochemical level understanding of eicosanoid metabolism would aid in understanding the mechanisms that govern inflammatory processes. Here, we present a combined experimental and computational approach to understanding the biochemical basis of eicosanoid metabolism in macrophages. Lipidomic and transcriptomic measurements and analyses reveal temporal and dynamic changes of the eicosanoid metabolic network in mouse bone marrow-derived macrophages (BMDM) upon stimulation of the Toll-like receptor 4 with Kdo2-Lipid A (KLA) and stimulation of the P2X7 purinergic receptor with adenosine 5'-triphosphate. Kinetic models were developed for the cyclooxygenase (COX) and lipoxygenase branches of arachidonic acid metabolism, and then the rate constants were estimated with a data set from ATP-stimulated BMDM, using a two-step matrix-based approach employing a constrained least-squares method followed by nonlinear optimization. The robustness of the model was validated through parametric sensitivity, uncertainty analysis, and predicting an independent dataset from KLA-primed ATP-stimulated BMDM by allowing the parameters to vary within the uncertainty range of the calculated parameters. We analyzed the functional coupling between COX isozymes and terminal enzymes by developing a PGH2-divided model. This provided evidence for the functional coupling between COX-2 and PGE2 synthase, between COX-1/COX-2 and PGD2 synthase, and also between COX-1 and thromboxane A2 synthase. Further, these functional couplings were experimentally validated using COX-1 and COX-2 selective inhibitors. The resulting fluxomics analysis demonstrates that the "multi-omics" systems biology approach can define the complex machinery of eicosanoid networks.

Indexed as

Models, BiologicalAdenosine TriphosphateAnimalsCells, CulturedCyclooxygenase 2 InhibitorsEicosanoidsIntramolecular OxidoreductasesKineticsLipocalinsLipopolysaccharidesLipoxygenaseMacrophagesMiceMice, Inbred C57BLProstaglandin-Endoperoxide SynthasesThromboxane-A SynthaseAdenosine TriphosphateCyclooxygenase 2 InhibitorsEicosanoidsIntramolecular OxidoreductasesKdo2-lipid ALipocalinsLipopolysaccharidesLipoxygenaseProstaglandin-Endoperoxide Synthasesprostaglandin R2 D-isomeraseThromboxane-A Synthase

Identifiers

PMID24559999
PMCPMC3945033
OpenAlexW1978221234

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.