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Cited by 185Gastrointestinal motility and disordersInflammatory Bowel DiseaseProtease and Inhibitor Mechanisms

Increased Proteasome-Mediated Degradation of Occludin in Irritable Bowel Syndrome

Coëffier, Moïse, Gloro, Romain, Boukhettala, Nabile, Aziz, Moutaz, Lecleire, Stéphane, Vandaele, Nathalie, Antonietti, Michel, Savoye, Guillaume +4 more·2010·American Journal of Gastroenterology
DOI 10.1038/ajg.2009.700
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Abstract

OBJECTIVES: Proteasome-mediated protein degradation may contribute to the regulation of intestinal inflammation. At the same time, low-grade inflammation and increased intestinal permeability seem to be involved in the pathophysiology of irritable bowel syndrome (IBS). Thus, we aimed to evaluate proteasome composition and activities in colonic mucosa of IBS patients and its putative pathogenic role. METHODS: Proteasome activities and proteasome subunit expression were measured in colonic mucosa of IBS, Crohn's disease (CD), and control patients by fluorometric assays and western blot, respectively. Expression of inhibitor of kappa B factor (IkappaB alpha) and occludin, a tight junction protein, was also evaluated in colonic biopsies. The degradation of recombinant occludin incubated with protein extracts from colonic mucosa was evaluated in the presence or absence of proteasome inhibitor, MG132. RESULTS: Proteasome trypsin-like activity was increased in IBS patients compared with CD and controls, whereas chymotrypsin-like activity was upregulated in CD patients only. Caspase-like activity was reduced both in IBS and CD patients. IkappaB alpha expression was similar between IBS and controls. In contrast, occludin expression was lower in IBS than in controls, but occludin mRNA level was similar. Protein extracts from IBS patients but not from controls degraded recombinant occludin (20% over 160 min), which was blocked by MG132. Although mast cell number was increased in IBS patients, no correlation was found between this number and proteasome alterations. CONCLUSIONS: Our study shows that proteasome alterations are present in the colonic mucosa of IBS patients and may contribute to the pathophysiology of IBS by increasing occludin degradation.

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Crossref · 10.1038/ajg.2009.700

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  • Expression levels of other tight junction proteins, such as JAM-A, occludin, and ZO-1, remain suppressed during intestinal inflammation.

    “Apart from claudins, expression levels of other TJ proteins, such as JAM-A, occludin, and ZO-1, remain suppressed during intestinal inflammation [194].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [194]

  • In one study, levels of TNF-α were elevated, but levels of IL-6 and interferon-γ were decreased in the mucosa of patients with IBS compared with controls.

    “Results from examination of cytokine protein levels have been conflicting. In one study, levels of TNF-α were elevated, but levels of IL-6 and interferon-γ were decreased in mucosa of patients with IBS compared with controls (41).”

    From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [41]

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Authors
Coëffier, M., Gloro, R., Boukhettala, N., Aziz, M., Lecleire, S., Vandaele, N., Antonietti, M., Savoye, G., Bôle-Feysot, C., Déchelotte, P., Reimund, J. M., & Ducrotté, P.
Affiliations
  • Centre Hospitalier Universitaire de Caen Normandie (FR)
  • Université de Rouen Normandie (FR)
  • Centre Hospitalier Universitaire de Rouen (FR)
ORCID
Venue
American Journal of Gastroenterology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2010-05
Volume
105
Issue
5
Pages
1181-1188
ISSN
0002-9270 (ISSN-L)
DOI
10.1038/ajg.2009.700
OpenAlex
W2076998894
Cited by
185
References
32
Citations by year
2026: 3 · 2025: 2 · 2024: 11 · 2023: 12 · 2022: 4 · 2021: 17 · 2020: 12 · 2019: 11 · 2018: 13 · 2017: 13 · 2016: 17 · 2015: 9 · 2014: 15 · 2013: 16 · 2012: 10
FWCI
10.62
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (unspecified)
Locations
  • The American Journal of Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
irritable bowel syndrome, proteasome, occludin, protein degradation, colonic mucosa, intestinal permeability, tight junctions, Crohn's disease, proteasome activity, caspase-like activity, IκBα, mast cells, low-grade intestinal inflammation
MeSH terms
Adult, Analysis of Variance, Biopsy, Needle, Cell Membrane Permeability, Crohn Disease, Female, Humans, Immunohistochemistry, Intestinal Mucosa, Male, Mast Cells, Membrane Proteins, Middle Aged, Probability, Reference Values, Sensitivity and Specificity, Severity of Illness Index, Blotting, Western, Case-Control Studies, Cytokines, Statistics, Nonparametric, Reverse Transcriptase Polymerase Chain Reaction, Irritable Bowel Syndrome, Proteasome Endopeptidase Complex, Young Adult, Occludin

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