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Papers In Press, published online ahead of print April 18, 2003
Department of Biopharmaceutics, Leiden University, Leiden, Zuid-Holland 2300 RA
Corresponding Author: hoekstra{at}lacdr.leidenuniv.nl
Hepatic cholesterol(ester) uptake from serum coupled to intracellular processing and biliary excretion are important features in the removal of excess cholesterol from the body. ATP-binding cassette (ABC) transporters play an important role in hepatic cholesterol transport. The liver consists of different cell types and ABC transporters may exert different physiological functions dependent on the individual cell type. Therefore, in the current study, we compared using real-time PCR the mRNA expression of ABC transporters and genes involved in the regulation of cholesterol metabolism in liver parenchymal, endothelial, and Kupffer cells. It appears that liver parenchymal cells contain high expression levels compared to endothelial and Kupffer cells of SR-BI (~3 fold), PPARalpha and PPARgamma (8-20 fold), CYP7A1 (>100 fold) and ABCG5/G8 (~5 fold). Liver endothelial cells show a high expression of CYP27, LXRbeta, PPARdelta and ABCG1, suggesting a novel specific role for these genes in endothelial cells. In Kupffer cells, the expression level of LXRalpha, ABCA1 and in particular ABCG1 is high leading to an ABCG1 mRNA expression level which is 70 fold higher than for parenchymal cells. It can be calculated that 51% of the total liver ABCG1 expression resides in Kupffer cells and 24% in endothelial cells, suggesting an intrahepatic specific role for ABCG1 in Kupffer and endothelial cells. Our data indicate that for studies on the role of ABC transporters and their regulation in liver, their cellular localization should be taken into account, allowing proper interpretation of metabolic changes, which are directly related to their (intra)cellular expression level.
J. Biol. Chem, 10.1074/jbc.M301189200
Submitted on February 4, 2003
Revised on April 7, 2003
Accepted on April 17, 2003
Specific gene expression of ATP-binding cassette transporters and nuclear hormone receptors in rat liver parenchymal, endothelial, and Kupffer cells
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