Evidence map›Paper›PMID 25675482›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Tetrahydrobiopterin and alkylglycerol monooxygenase substantially alter the murine macrophage lipidome.

Katrin Watschinger, Markus A Keller, Eileen McNeill, Mohammad T Alam, Steven Lai, Sabrina Sailer, Veronika Rauch, Jyoti Patel, Albin Hermetter, Georg Golderer and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

36 citing papers in PubMed, 62 citations in OpenAlex.

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  10. Multiple Shades of Gray-Macrophages in Acute Allograft Rejection.International journal of molecular sciences · 2023
    Review
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  14. Review
  15. Article
  16. Sapropterin (BH4) Aggravates Autoimmune Encephalomyelitis in Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021
    Observational
  17. Article
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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

17 authors at 6 institutions in 3 countries.

Katrin WatschingerDivision of Biological Chemistry, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria; katrin.watschinger@i-med.ac.at ernst.r.werner@i-med.ac.at.ORCID http://orcid.org/0000-0002-1122-8444
Markus A KellerDivision of Biological Chemistry, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria; Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, United Kingdom;
Eileen McNeillDivision of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom;
Mohammad T AlamDepartment of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, United Kingdom;
Steven LaiWaters Corporation, Milford, MA 01757;
Sabrina SailerDivision of Biological Chemistry, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria;
Veronika RauchDivision of Molecular Pathophysiology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria;
Jyoti PatelDivision of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom;
Albin HermetterInstitute of Biochemistry, Graz University of Technology, 8010 Graz, Austria;
Georg GoldererDivision of Biological Chemistry, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria;
Stephan GeleyDivision of Molecular Pathophysiology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria;
Gabriele Werner-FelmayerDivision of Biological Chemistry, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria;
Robert S PlumbDepartment of Surgery and Cancer, Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom;
Giuseppe AstaritaWaters Corporation, Milford, MA 01757; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057-1468; and.
Markus RalserDepartment of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge CB2 1GA, United Kingdom; Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom.
Keith M ChannonDivision of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom;
Ernst R WernerDivision of Biological Chemistry, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria; katrin.watschinger@i-med.ac.at ernst.r.werner@i-med.ac.at.
Innsbruck Medical University · ATJohn Radcliffe Hospital · GBUniversity of Cambridge · GBWaters (United States) · USGraz University of Technology · ATImperial College London · GB

Funding

Austrian Science Fund FWF P 22406British Heart Foundation RE/08/004/23915British Heart Foundation RG/07/003/23133British Heart Foundation RG/12/5/29576Wellcome Trust 090532
6 · The paper itself

Abstract

Tetrahydrobiopterin is a cofactor synthesized from GTP with well-known roles in enzymatic nitric oxide synthesis and aromatic amino acid hydroxylation. It is used to treat mild forms of phenylketonuria. Less is known about the role of tetrahydrobiopterin in lipid metabolism, although it is essential for irreversible ether lipid cleavage by alkylglycerol monooxygenase. Here we found intracellular alkylglycerol monooxygenase activity to be an important regulator of alkylglycerol metabolism in intact murine RAW264.7 macrophage-like cells. Alkylglycerol monooxygenase was expressed and active also in primary mouse bone marrow-derived monocytes and "alternatively activated" M2 macrophages obtained by interleukin 4 treatment, but almost missing in M1 macrophages obtained by IFN-γ and lipopolysaccharide treatment. The cellular lipidome of RAW264.7 was markedly changed in a parallel way by modulation of alkylglycerol monooxygenase expression and of tetrahydrobiopterin biosynthesis affecting not only various ether lipid species upstream of alkylglycerol monooxygenase but also other more complex lipids including glycosylated ceramides and cardiolipins, which have no direct connection to ether lipid pathways. Alkylglycerol monooxygenase activity manipulation modulated the IFN-γ/lipopolysaccharide-induced expression of inducible nitric oxide synthase, interleukin-1β, and interleukin 1 receptor antagonist but not transforming growth factor β1, suggesting that alkylglycerol monooxygenase activity affects IFN-γ/lipopolysaccharide signaling. Our results demonstrate a central role of tetrahydrobiopterin and alkylglycerol monooxygenase in ether lipid metabolism of murine macrophages and reveal that alteration of alkylglycerol monooxygenase activity has a profound impact on the lipidome also beyond the class of ether lipids.

Indexed as

AnimalsBiopterinsBone Marrow CellsCell DifferentiationCell LineCells, CulturedCluster AnalysisGene Knockdown TechniquesGTP CyclohydrolaseInterferon-gammaLentivirusLipid MetabolismLipopolysaccharidesMacrophagesMiceMixed Function OxygenasesBiopterinsglyceryl-ether monooxygenaseGTP CyclohydrolaseInterferon-gammaLipopolysaccharidesMixed Function OxygenasesNitric Oxide Synthase Type IIsapropterinalkylglycerolslipidomicsmacrophagesRAW264.7tetrahydrobiopterin

Identifiers

PMID25675482
PMCPMC4345615
OpenAlexW2112828311

What OpenQuestion holds

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Registered trials

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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.