Document Detail


Functional analysis of candidate ABC transporter proteins for sitosterol transport.
MedLine Citation:
PMID:  12488046     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Two ATP-binding cassette (ABC) proteins, ABCG5 and ABCG8, have recently been associated with the accumulation of dietary cholesterol in the sterol storage disease sitosterolemia. These two 'half-transporters' are assumed to dimerize to form the complete sitosterol transporter which reduces the absorption of sitosterol and related molecules in the intestine by pumping them back into the lumen. Although mutations altering ABCG5 and ABCG8 are found in affected patients, no functional demonstration of sitosterol transport has been achieved. In this study, we investigated whether other ABC transporters implicated in lipid movement and expressed in tissues with a role in sterol synthesis and absorption, might also be involved in sitosterol transport. Transport by the multidrug resistance P-glycoprotein (P-gp; Abcb1), the multidrug resistance-associated protein (Mrp1; Abcc1), the breast cancer resistance protein (Bcrp; Abcg2) and the bile salt export pump (Bsep; Abcb11) was assessed using several assays. Unexpectedly, none of the candidate proteins mediated significant sitosterol transport. This has implications for the pathology of sitosterolemia. In addition, the data suggest that otherwise broad-specific ABC transporters have acquired specificity to exclude sitosterol and related sterols like cholesterol presumably because the abundance of cholesterol in the membrane would interfere with their action; in consequence, specific transporters have evolved to handle these sterols.
Authors:
C Albrecht; J I Elliott; A Sardini; T Litman; B Stieger; P J Meier; C F Higgins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1567     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-18     Completed Date:  2003-02-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  133-42     Citation Subset:  IM    
Affiliation:
MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Rd., London W12 ONN, UK. c.albrecht@csc.mrc.ac.uk
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
ATP-Binding Cassette Transporters / metabolism*
Animals
Biological Transport
Flow Cytometry
Mice
Mice, Knockout
Microscopy, Confocal
Multidrug Resistance-Associated Proteins / metabolism
Neoplasm Proteins*
P-Glycoprotein / metabolism
Sitosterols / metabolism*
Spodoptera
Chemical
Reg. No./Substance:
0/ABCG2 protein, human; 0/ATP-Binding Cassette Transporters; 0/Multidrug Resistance-Associated Proteins; 0/Neoplasm Proteins; 0/P-Glycoprotein; 0/Sitosterols; 0/multidrug resistance-associated protein 1; 5779-62-4/sitosterol

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