Increased proteasome-mediated degradation of occludin in irritable bowel syndrome

Am J Gastroenterol. 2010 May;105(5):1181-8. doi: 10.1038/ajg.2009.700. Epub 2009 Dec 8.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Biopsy, Needle
  • Blotting, Western
  • Case-Control Studies
  • Cell Membrane Permeability / physiology
  • Crohn Disease / metabolism
  • Crohn Disease / pathology
  • Cytokines / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Irritable Bowel Syndrome / metabolism*
  • Irritable Bowel Syndrome / pathology
  • Male
  • Mast Cells / cytology
  • Mast Cells / physiology
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Occludin
  • Probability
  • Proteasome Endopeptidase Complex / metabolism*
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Young Adult


  • Cytokines
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Proteasome Endopeptidase Complex