Document Detail

Depletion of Caco-2 cell cholesterol disrupts barrier function by altering the detergent solubility and distribution of specific tight-junction proteins.
MedLine Citation:
PMID:  15500448     Owner:  NLM     Status:  MEDLINE    
In the present study, we have investigated the role of cholesterol in maintaining the barrier properties of the model intestinal cell line Caco-2. We have extracted membrane cholesterol using methyl-beta-cyclodextrin and demonstrated that maximally, methyl-beta-cyclodextrin lowered cell cholesterol levels by 40-45%. Depletion of cell cholesterol was accompanied by an 80-90% decrease in monolayer transepithelial electrical resistance and a significant increase in the paracellular permeability of dextrans of 4, 10 and 40 kDa. The increase in dextran permeability was most pronounced for the two lower molecular mass species. In addition to the decline in the barrier properties of the monolayers, extraction of cell cholesterol produced an increase in the Triton X-100 solubility of claudin 3, claudin 4 and occludin, and the loss of all three proteins from the plasma membrane (tight junctions). In contrast, removal of cholesterol had no detectable influence on the detergent solubility or morphological distribution of claudin 1. These results indicate that membrane cholesterol is a critical factor in maintaining the barrier property of epithelial monolayers. More specifically, cholesterol appears to stabilize the association of certain proteins with the tight junctions.
Daniel Lambert; Catherine A O'Neill; Philip J Padfield
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  387     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-01     Completed Date:  2005-10-20     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  553-60     Citation Subset:  IM    
Division of Gastrointestinal Science, University of Manchester, Hope Hospital, Salford M6 8HD, UK.
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MeSH Terms
Caco-2 Cells
Cholesterol / chemistry,  physiology*
Electric Impedance
Intestinal Mucosa / chemistry,  physiology*
Membrane Microdomains / chemistry,  physiology
Membrane Proteins / chemistry,  physiology*
Tight Junctions / physiology*
Time Factors
Reg. No./Substance:
0/CLDN1 protein, human; 0/CLDN3 protein, human; 0/CLDN4 protein, human; 0/Claudin-1; 0/Claudin-3; 0/Claudin-4; 0/Detergents; 0/Membrane Proteins; 0/OCLN protein, human; 0/Occludin; 0/beta-Cyclodextrins; 0/flotillins; 0/methyl-beta-cyclodextrin; 57-88-5/Cholesterol; 9002-93-1/Octoxynol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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