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

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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, Bôle-Feysot, Christine, Déchelotte, Pierre, Reimund, Jean Marie, Ducrotté, Philippe·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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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: Savoye, Guillaume
Déchelotte, Pierre
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
Health Sciences › Medicine › Gastroenterology › 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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Increased Proteasome-Mediated Degradation of Occludin in Irritable Bowel Syndrome

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