title: Hepatic cell-specific ATP-binding cassette (ABC) transporter profiling identifies putative novel candidates for lipid homeostasis in mice.
abstract: 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.
authors.affiliation: 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
authors.forename: Dan
authors.initials: D
authors.lastname: Ye
authors.forename: Menno
authors.initials: M
authors.lastname: Hoekstra
authors.forename: Ruud
authors.initials: R
authors.lastname: Out
authors.forename: Illiana
authors.initials: I
authors.lastname: Meurs
authors.forename: J Kar
authors.initials: JK
authors.lastname: Kruijt
authors.forename: Reeni B
authors.initials: RB
authors.lastname: Hildebrand
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: Van Berkel
authors.forename: Miranda
authors.initials: M
authors.lastname: Van Eck
mesh_terms: 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
chemical_list: D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol