Evidence map›Paper›PMID 25368325›Full record

ArticleThe Journal of biological chemistry2014

Systemic blockade of sialylation in mice with a global inhibitor of sialyltransferases.

Matthew S Macauley, Britni M Arlian, Cory D Rillahan, Poh-Choo Pang, Nikki Bortell, Maria Cecilia G Marcondes, Stuart M Haslam, Anne Dell, James C Paulson

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

70 citing papers in PubMed, 124 citations in OpenAlex.

  1. Review
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  10. Sialylation Inhibition Impairs Migration and Promotes Adhesion of GBM Cells.International journal of molecular sciences · 2025
    Article
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  12. Review
  13. Adhesion to aggression: unravelling sLeClinical & experimental metastasis · 2025
    Review
  14. Article
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10 more citing papers are in PubMed but not listed here.

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 2 institutions in 2 countries.

Matthew S MacauleyFrom the Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science and.
Britni M ArlianFrom the Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science and.
Cory D RillahanFrom the Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science and the Division of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, and.
Poh-Choo Pangthe Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
Nikki Bortellthe Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La, Jolla, California 92037.
Maria Cecilia G Marcondesthe Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La, Jolla, California 92037.
Stuart M Haslamthe Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
Anne Dellthe Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
James C PaulsonFrom the Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science and jpaulson@scripps.edu.
Imperial College London · GBScripps Research Institute · US

Funding

Treating lung inflammation by targeting SiglecsP01HL107151 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI SCHNAAR, RONALD L · 2011 to 2017
$15.4M
REGULATION OF SIALOSIDE EXPRESSION IN LEUKOCYTESR01AI050143 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI PAULSON, JAMES C · 2003 to 2018
$7.0M
Methamphetamine and HIV interactions in the regulation of glial activationR01DA036164 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI MARCONDES, MARIA CECILIA GARIBALDI · 2013 to 2017
$2.4M
Biotechnology and Biological Sciences Research Council BB/F008309/1Biotechnology and Biological Sciences Research Council BB/K016164/1NHLBI NIH HHS HL107151NHLBI NIH HHS P01 HL107151NIAID NIH HHS R01 AI050143NIDA NIH HHS R01 DA036164
6 · The paper itself

Abstract

Sialic acid terminates glycans of glycoproteins and glycolipids that play numerous biological roles in health and disease. Although genetic tools are available for interrogating the effects of decreased or abolished sialoside expression in mice, pharmacological inhibition of the sialyltransferase family has, to date, not been possible. We have recently shown that a sialic acid analog, 2,4,7,8,9-pentaacetyl-3Fax-Neu5Ac-CO2Me (3F-NeuAc), added to the media of cultured cells shuts down sialylation by a mechanism involving its intracellular conversion to CMP-3F-NeuAc, a competitive inhibitor of all sialyltransferases. Here we show that administering 3F-NeuAc to mice dramatically decreases sialylated glycans in cells of all tissues tested, including blood, spleen, liver, brain, lung, heart, kidney, and testes. A single dose results in greatly decreased sialoside expression for over 7 weeks in some tissues. Although blockade of sialylation with 3F-NeuAc does not affect viability of cultured cells, its use in vivo has a deleterious "on target" effect on liver and kidney function. After administration of 3F-NeuAc, liver enzymes in the blood are dramatically altered, and mice develop proteinuria concomitant with dramatic loss of sialic acid in the glomeruli within 4 days, leading to irreversible kidney dysfunction and failure to thrive. These results confirm a critical role for sialosides in liver and kidney function and document the feasibility of pharmacological inhibition of sialyltransferases for in vivo modulation of sialoside expression.

Indexed as

AnimalsBlotting, WesternBrainDose-Response Relationship, DrugEnzyme InhibitorsFlow CytometryGlycolipidsGlycoproteinsKidneyLeukocytesLiverLungMaleMass SpectrometryMice, Inbred C57BLMyocardium2,4,7,8,9-pentaacetyl-3Fax-NeuCO2MEnzyme InhibitorsGlycolipidsGlycoproteinsN-Acetylneuraminic AcidPolysaccharidesSialic AcidsSialyltransferasesGlycosylation InhibitorGlycosyltransferaseKidneyPodocyteSialic AcidSialyltransferase

Identifiers

PMID25368325
PMCPMC4271204
OpenAlexW2126381976

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.