Evidence map›Paper›PMID 24850807›Full record

ArticleJournal of lipid research2014

Selective inhibitors of a PAF biosynthetic enzyme lysophosphatidylcholine acyltransferase 2.

Megumi Tarui, Hideo Shindou, Kazuo Kumagai, Ryo Morimoto, Takeshi Harayama, Tomomi Hashidate, Hirotatsu Kojima, Takayoshi Okabe, Tetsuo Nagano, Takahide Nagase and 1 more

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

Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

20 citing papers in PubMed, 34 citations in OpenAlex.

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  10. Mutagenesis and homology modeling reveal a predicted pocket of lysophosphatidylcholine acyltransferase 2 to catch Acyl-CoA.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
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  18. Relief from neuropathic pain by blocking of the platelet-activating factor-pain loop.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
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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

11 authors at 3 institutions in 1 country.

Megumi TaruiDepartment of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan Department of Respiratory Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Hideo ShindouDepartment of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
Kazuo KumagaiOpen Innovation Center for Drug Discovery, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Ryo MorimotoDepartment of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Takeshi HarayamaDepartment of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan.
Tomomi HashidateDepartment of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan.
Hirotatsu KojimaOpen Innovation Center for Drug Discovery, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Takayoshi OkabeOpen Innovation Center for Drug Discovery, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Tetsuo NaganoOpen Innovation Center for Drug Discovery, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Takahide NagaseDepartment of Respiratory Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Takao ShimizuDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
The University of Tokyo · JPNational Center for Global Health and Medicine · JPThe Open University of Japan · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Platelet-activating factor (PAF) is a potent pro-inflammatory phospholipid mediator. In response to extracellular stimuli, PAF is rapidly biosynthesized by lyso-PAF acetyltransferase (lyso-PAFAT). Previously, we identified two types of lyso-PAFATs: lysophosphatidylcholine acyltransferase (LPCAT)1, mostly expressed in the lungs where it produces PAF and dipalmitoyl-phosphatidylcholine essential for respiration, and LPCAT2, which biosynthesizes PAF and phosphatidylcholine (PC) in the inflammatory cells. Under inflammatory conditions, LPCAT2, but not LPCAT1, is activated and upregulated to produce PAF. Thus, it is important to develop inhibitors specific for LPCAT2 in order to ameliorate PAF-related inflammatory diseases. Here, we report the first identification of LPCAT2-specific inhibitors, N-phenylmaleimide derivatives, selected from a 174,000-compound library using fluorescence-based high-throughput screening followed by the evaluation of the effects on LPCAT1 and LPCAT2 activities, cell viability, and cellular PAF production. Selected compounds competed with acetyl-CoA for the inhibition of LPCAT2 lyso-PAFAT activity and suppressed PAF biosynthesis in mouse peritoneal macrophages stimulated with a calcium ionophore. These compounds had low inhibitory effects on LPCAT1 activity, indicating that adverse effects on respiratory functions may be avoided. The identified compounds and their derivatives will contribute to the development of novel drugs for PAF-related diseases and facilitate the analysis of LPCAT2 functions in phospholipid metabolism in vivo.

Indexed as

1-Acylglycerophosphocholine O-AcyltransferaseAcetyltransferasesAnimalsEnzyme InhibitorsMacrophages, PeritonealMicePlatelet Activating FactorRAW 264.7 Cells1-Acylglycerophosphocholine O-Acyltransferase1-alkylglycerophosphocholine acetyltransferaseAcetyltransferasesEnzyme InhibitorsLpcat1 protein, mouseLPCAT2 protein, mousePlatelet Activating Factorfluorescent probehigh-throughput screeninginflammationlipid mediatorLPCAT2 inhibitorlyso-PAF acetyltransferaselysophospholipid acyltransferaseN-phenylmaleimide derivativesplatelet-activating factorTSI-01

Identifiers

PMID24850807
PMCPMC4076079
OpenAlexW2122938153

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.