Hepatic cell-specific ATP-binding cassette (ABC) transporter profiling identifies putative novel candidates for lipid homeostasis in mice.
BACKGROUND
ABC-transporters play an important role in lipid trafficking. Therefore, hepatic expression patterns of ABC-transporters involved in the regulation of cholesterol metabolism were evaluated.


RESULTS
RT-PCR analysis showed that the mRNA expression of 38 ABC-transporters detected in livers of C57Bl/6 mice varied greatly. Although most ABC-transporters were ubiquitously expressed, some members displayed very restricted expression patterns, e.g. ABCA6, A8, B1, B8, B10, B11, C3, D2, and G5/G8 were exclusively (>99%) expressed in parenchymal cells. Interestingly, another 13 ABC-transporters, including ABCA4, A5, A9, A13, B2, B9, C1, C5, D3, D4, F2, G1, and G4 were primarily expressed in Kupffer cells. Although Kupffer cells only contribute to 2.5% of the total liver protein, these 13 genes did contain 9-27% of the total liver expression. Western-type diet feeding (0.25% cholesterol, 15% fat) induced the expression of several primarily Kupffer cell expressed genes, including ABCA5, B9, D3, and D4 (2 to 3-fold higher), whereas the other ABC-transporters were not significantly changed.


CONCLUSIONS
Our findings underscore the importance of cellular localization for studying the regulation of key ABC-transporters in liver cholesterol homeostasis. Furthermore, several novel ABC-transporters, including ABCA5, B9, D3, and D4 were identified as putative novel candidates involved in liver macrophage cholesterol homeostasis.
Ye
Dan
D
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. y.dan@chem.leidenuniv.nl
Hoekstra
Menno
M
Out
Ruud
R
Meurs
Illiana
I
Kruijt
J Kar
JK
Hildebrand
Reeni B
RB
Van Berkel
Theo J C
TJ
Van Eck
Miranda
M
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D004032:Diet; D020869:Gene Expression Profiling; D006706:Homeostasis; D007728:Kupffer Cells / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice
D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol