Evidence map›Paper›PMID 27226251›Full record

ArticleGlycobiology2016

The NEU1-selective sialidase inhibitor, C9-butyl-amide-DANA, blocks sialidase activity and NEU1-mediated bioactivities in human lung in vitro and murine lung in vivo.

Sang W Hyun, Anguo Liu, Zhenguo Liu, Alan S Cross, Avelino C Verceles, Sadagopan Magesh, Yadagiri Kommagalla, Chandrababunaidu Kona, Hiromune Ando, Irina G Luzina and 7 more

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

Article in Glycobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 2 pooled it
1.6field-weighted citation impact, top 17% 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

31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
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  6. Review
  7. Article
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  9. iScience · 2024
    Article
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  13. Article
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  15. Article
  16. Sialidase Inhibitors with Different Mechanisms.Journal of medicinal chemistry · 2022
    Review
  17. Review
  18. Article
  19. 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 4 institutions in 2 countries.

Sang W HyunBaltimore Veterans Affairs Medical Center, 10 North Greene Street, Baltimore, MD 21201, USA Department of Medicine.
Anguo LiuBaltimore Veterans Affairs Medical Center, 10 North Greene Street, Baltimore, MD 21201, USA Department of Medicine.
Zhenguo LiuBaltimore Veterans Affairs Medical Center, 10 North Greene Street, Baltimore, MD 21201, USA.
Alan S CrossDepartment of Medicine Center for Vaccine Development, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
Avelino C VercelesDepartment of Medicine.
Sadagopan MageshDepartment of Applied Bio-organic Chemistry, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Yadagiri KommagallaDepartment of Applied Bio-organic Chemistry, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Chandrababunaidu KonaDepartment of Applied Bio-organic Chemistry, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
Hiromune AndoDepartment of Applied Bio-organic Chemistry, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
Irina G LuzinaBaltimore Veterans Affairs Medical Center, 10 North Greene Street, Baltimore, MD 21201, USA Department of Medicine.
Sergei P AtamasBaltimore Veterans Affairs Medical Center, 10 North Greene Street, Baltimore, MD 21201, USA Department of Medicine Department of Microbology and Immunology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
Kurt H PiepenbrinkDepartment of Medicine Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard St, Baltimore, MD 21201, USA.
Eric J SundbergDepartment of Medicine Department of Microbology and Immunology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard St, Baltimore, MD 21201, USA.
Wei GuangDepartment of Pediatrics, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
Hideharu IshidaDepartment of Applied Bio-organic Chemistry, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Erik P LillehojDepartment of Pediatrics, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
Simeon E GoldblumBaltimore Veterans Affairs Medical Center, 10 North Greene Street, Baltimore, MD 21201, USA Center for Vaccine Development, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA sgoldblu@mbrc.umaryland.edu.
University of Maryland, Baltimore · USVeterans Health Administration · USGifu University · JPKyoto University · JP

Funding

Molecular basis of ADCC-mediated HIV protectionR01AI090866 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI SUNDBERG, ERIC JOHN · 2010 to 2013
$2.2M
The Mechanisms of Profibrotic Sensitization by IL33R01HL126897 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI LUZINA, IRINA G. · 2015 to 2018
$1.4M
Structure and Function of Type IV Pili in Clostridium difficileF32AI110045 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI PIEPENBRINK, KURT HENRY · 2014 to 2015
$109k
NEU1 Sialidase Disrupts CD31-Driven Angiogenesis in Human Lung EndotheliaI01BX002352 · VA · BALTIMORE VA MEDICAL CENTER · PI GOLDBLUM, SIMEON EMANUEL · 2015 to 2018
–
The Central Role of IL-33 in Immune-Mediated ScarringI01BX002499 · VA · BALTIMORE VA MEDICAL CENTER · PI LUZINA, IRINA G. · 2015 to 2020
–
Integrin-dependent mechanism of T cell-mediated pulmonary fibrosisI01CX000101 · VA · BALTIMORE VA MEDICAL CENTER · PI LUZINA, IRINA G. · 2009 to 2017
–
BLRD VA I01 BX002352BLRD VA I01 BX002499CSRD VA I01 CX000101NHLBI NIH HHS R01 HL126897NIAID NIH HHS F32 AI110045NIAID NIH HHS R01 AI090866
6 · The paper itself

Abstract

Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung microvascular endothelia where it mediates multiple biological processes. We tested whether the NEU1-selective sialidase inhibitor, C9-butyl-amide-2-deoxy-2,3-dehydro-N-acetylneuraminic acid (C9-BA-DANA), inhibits one or more established NEU1-mediated bioactivities in human lung cells. We established the IC50 values of C9-BA-DANA for total sialidase activity in human airway epithelia, lung microvascular endothelia and lung fibroblasts to be 3.74 µM, 13.0 µM and 4.82 µM, respectively. In human airway epithelia, C9-BA-DANA dose-dependently inhibited flagellin-induced, NEU1-mediated mucin-1 ectodomain desialylation, adhesiveness for Pseudomonas aeruginosa and shedding. In lung microvascular endothelia, C9-BA-DANA reversed NEU1-driven restraint of cell migration into a wound and disruption of capillary-like tube formation. NEU1 and its chaperone/transport protein, protective protein/cathepsin A (PPCA), were differentially expressed in these same cells. Normalized NEU1 protein expression correlated with total sialidase activity whereas PPCA expression did not. In contrast to eukaryotic sialidases, C9-BA-DANA exerted far less inhibitory activity for three selected bacterial neuraminidases (IC50 > 800 µM). Structural modeling of the four human sialidases and three bacterial neuraminidases revealed a loop between the seventh and eighth strands of the β-propeller fold, that in NEU1, was substantially shorter than that seen in the six other enzymes. Predicted steric hindrance between this loop and C9-BA-DANA could explain its selectivity for NEU1. Finally, pretreatment of mice with C9-BA-DANA completely protected against flagellin-induced increases in lung sialidase activity. Our combined data indicate that C9-BA-DANA inhibits endogenous and ectopically expressed sialidase activity and established NEU1-mediated bioactivities in human airway epithelia, lung microvascular endothelia, and fibroblasts in vitro and murine lungs in vivo.

Indexed as

AnimalsBacterial ProteinsCathepsin ACell MovementEndothelial CellsEndothelium, VascularEnzyme InhibitorsEpithelial CellsFibroblastsFlagellinGene Expression RegulationHumansHydrolysisIsoenzymesLungMiceBacterial ProteinsCathepsin ACTSA protein, humanEnzyme InhibitorsFlagellinIsoenzymesMucin-1N-Acetylneuraminic AcidNEU1 protein, humanNeuraminidaselungNEU1neuraminidasePPCAsialidase

Identifiers

PMID27226251
PMCPMC5884327
OpenAlexW2405781470

What OpenQuestion holds

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Read underepoch 390

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.