Document Detail

Influence of thiol balance on micellar cholesterol handling by polarized Caco-2 intestinal cells.
MedLine Citation:
PMID:  12965223     Owner:  NLM     Status:  MEDLINE    
The in vitro thiol redox modulation of cholesterol homeostasis was investigated in polarized Caco-2 intestinal cells. Cells were pre-incubated with the pro-oxidant compound CuSO4 or with the antioxidant N-acetylcysteine (NAC), to induce a mild shift of the intracellular redox potential toward, respectively, a more oxidizing or a more reducing equilibrium, via a manipulation of intracellular soluble thiols (glutathione). Then, monolayers were exposed to micellar cholesterol and both the cholesterol uptake and export, as well as the cholesteryl ester cycle, were analyzed. We found that pro-oxidizing conditions induced a significant cholesterol retention within the cells, particularly in the unesterified form (FC), as a result of an augmented sterol incorporation coupled with a reduced rate of FC esterification. A reduction in FC export was also evident. Furthermore, the combination of FC retention and the oxidative imbalance leads to significant alterations of the monolayer integrity, evidenced by both the enhanced tight junction permeability and the lactate dehydrogenase release into the basolateral medium. In contrast, a more reducing environment generated by NAC pre-treatment favors the limitation of the resident time of FC into the cells, via a reduced cholesterol uptake and a concomitant increased cholesterol esterification. In addition, a significant higher FC extrusion into the basolateral medium was also appreciable. Our results indicate that the thiol balance of intestinal cells may be critical for the regulation of cholesterol homeostasis at the intestinal level, influencing the lipid transport throughout the intestinal barrier.
Mariarosaria Napolitano; Gabriella Rainaldi; Elena Bravo; Roberto Rivabene
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  FEBS letters     Volume:  551     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-10     Completed Date:  2003-11-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  165-70     Citation Subset:  IM    
Laboratory of Metabolism and Pathological Biochemistry, Istituto Superiore di Sanità, 00161 Rome, Italy.
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MeSH Terms
Biological Transport
Caco-2 Cells
Cell Membrane Permeability
Cell Polarity
Cholesterol / metabolism*
Cholesterol Esters / metabolism
Glutathione / metabolism*
Intestinal Mucosa / metabolism*,  ultrastructure
Sulfhydryl Compounds / metabolism
Reg. No./Substance:
0/Cholesterol Esters; 0/Micelles; 0/Sulfhydryl Compounds; 57-88-5/Cholesterol; 70-18-8/Glutathione

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

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