Evidence map›Paper›PMID 30401902›Full record

ArticleScientific reports2018

A chemical genetic screen reveals that iminosugar inhibitors of plant glucosylceramide synthase inhibit root growth in Arabidopsis and cereals.

Michael D Rugen, Mathieu M J L Vernet, Laila Hantouti, Amalia Soenens, Vasilios M E Andriotis, Martin Rejzek, Paul Brett, Richard J B H N van den Berg, Johannes M F G Aerts, Hermen S Overkleeft and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

4 citing papers in PubMed, 10 citations in OpenAlex.

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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 3 countries.

Michael D RugenDepartment of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.
Mathieu M J L VernetDepartment of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.
Laila HantoutiDepartment of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.
Amalia SoenensDepartment of Metabolic Biology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.
Vasilios M E AndriotisDepartment of Metabolic Biology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.
Martin RejzekDepartment of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.ORCID http://orcid.org/0000-0002-5091-544X
Paul BrettDepartment of Metabolic Biology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.
Richard J B H N van den BergLeiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
Johannes M F G AertsDepartment of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.
Hermen S OverkleeftLeiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, 2300 RA, Leiden, The Netherlands.
Robert A FieldDepartment of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK. Rob.Field@jic.ac.uk.
John Innes Centre · GBLeiden University · NLAmsterdam UMC Location University of Amsterdam · NL

Funding

Biotechnology and Biological Sciences Research Council BB/J500069/1Biotechnology and Biological Sciences Research Council BBS/E/J/000C0618
6 · The paper itself

Abstract

Iminosugars are carbohydrate mimics that are useful as molecular probes to dissect metabolism in plants. To analyse the effects of iminosugar derivatives on germination and seedling growth, we screened a library of 390 N-substituted iminosugar analogues against Arabidopsis and the small cereal Eragrostis tef (Tef). The most potent compound identified in both systems, N-5-(adamantane-1-yl-ethoxy)pentyl- L-ido-deoxynojirimycin (L-ido-AEP-DNJ), inhibited root growth in agar plate assays by 92% and 96% in Arabidopsis and Tef respectively, at 10 µM concentration. Phenocopying the effect of L-ido-AEP-DNJ with the commercial inhibitor (PDMP) implicated glucosylceramide synthase as the target responsible for root growth inhibition. L-ido-AEP-DNJ was twenty-fold more potent than PDMP. Liquid chromatography-mass spectrometry (LC-MS) analysis of ceramide:glucosylceramide ratios in inhibitor-treated Arabidopsis seedlings showed a decrease in the relative quantity of the latter, confirming that glucosylceramide synthesis is perturbed in inhibitor-treated plants. Bioinformatic analysis of glucosylceramide synthase indicates gene conservation across higher plants. Previous T-DNA insertional inactivation of glucosylceramide synthase in Arabidopsis caused seedling lethality, indicating a role in growth and development. The compounds identified herein represent chemical alternatives that can overcome issues caused by genetic intervention. These inhibitors offer the potential to dissect the roles of glucosylceramides in polyploid crop species.

Indexed as

AnimalsArabidopsisDrug Evaluation, PreclinicalEdible GrainEnzyme InhibitorsEragrostisGlucosylceramidesGlucosyltransferasesPlant RootsSugarsceramide glucosyltransferaseEnzyme InhibitorsGlucosylceramidesGlucosyltransferasesSugars

Identifiers

PMID30401902
PMCPMC6219604
OpenAlexW2898642681

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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.