Functional analysis of candidate ABC transporter proteins for sitosterol transport
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Functional analysis of candidate ABC transporter proteins for sitosterol transport. / Albrecht, C; Elliott, J I; Sardini, A; Litman, Thomas; Stieger, B; Meier, P J; Higgins, C F.
I: BBA General Subjects, Bind 1567, Nr. 1-2, 23.12.2002, s. 133-42.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Functional analysis of candidate ABC transporter proteins for sitosterol transport
AU - Albrecht, C
AU - Elliott, J I
AU - Sardini, A
AU - Litman, Thomas
AU - Stieger, B
AU - Meier, P J
AU - Higgins, C F
PY - 2002/12/23
Y1 - 2002/12/23
N2 - 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.
AB - 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.
KW - 3T3 Cells
KW - ATP-Binding Cassette Transporters
KW - Animals
KW - Biological Transport
KW - Flow Cytometry
KW - Mice
KW - Mice, Knockout
KW - Microscopy, Confocal
KW - Multidrug Resistance-Associated Proteins
KW - Neoplasm Proteins
KW - P-Glycoprotein
KW - Sitosterols
KW - Spodoptera
M3 - Journal article
C2 - 12488046
VL - 1567
SP - 133
EP - 142
JO - B B A - General Subjects
JF - B B A - General Subjects
SN - 0304-4165
IS - 1-2
ER -
ID: 119646625