Document Detail

Increased proteasome-mediated degradation of occludin in irritable bowel syndrome.
MedLine Citation:
PMID:  19997094     Owner:  NLM     Status:  MEDLINE    
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.
Mo?se Co?ffier; Romain Gloro; Nabile Boukhettala; Moutaz Aziz; St?phane Lecleire; Nathalie Vandaele; Michel Antonietti; Guillaume Savoye; Christine B?le-Feysot; Pierre D?chelotte; Jean Marie Reimund; Philippe Ducrott?
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-08
Journal Detail:
Title:  The American journal of gastroenterology     Volume:  105     ISSN:  1572-0241     ISO Abbreviation:  Am. J. Gastroenterol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-06     Completed Date:  2010-06-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0421030     Medline TA:  Am J Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1181-8     Citation Subset:  IM    
Nutrition Unit, Rouen University Hospital, Rouen, France.
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MeSH Terms
Analysis of Variance
Biopsy, Needle
Blotting, Western
Case-Control Studies
Cell Membrane Permeability / physiology
Crohn Disease / metabolism,  pathology
Cytokines / metabolism
Intestinal Mucosa / metabolism*,  pathology
Irritable Bowel Syndrome / metabolism*,  pathology
Mast Cells / cytology,  physiology
Membrane Proteins / metabolism*
Middle Aged
Proteasome Endopeptidase Complex / metabolism*
Reference Values
Reverse Transcriptase Polymerase Chain Reaction
Sensitivity and Specificity
Severity of Illness Index
Statistics, Nonparametric
Young Adult
Reg. No./Substance:
0/Cytokines; 0/Membrane Proteins; 0/occludin; EC Endopeptidase Complex

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