LXR-agonists regulate ApoM expression differentially in liver and intestine.
Apolipoprotein M (apoM) has been suggested to play a role in reverse cholesterol transport. Here we studied the influence of liver X-receptor (LXR) agonist on the transcriptional regulation of apoM. Studies were performed in murine liver and intestinal mucosal cells in vivo and in human intestinal Caco-2 cells in vitro. The expression of apoM was analyzed by quantitative real time PCR, and compared to well-established LXR target genes. Mice fed with TO901317 for six days showed a downregulation of apoM and apoAI in the liver to 40 % and 60 % respectively and an upregulation of Cyp7A1 to 280 %. In the small intestine, however, apoM and apoAI were upregulated by 30-60 % and ABCA1 by 250-430 %. In Caco-2 cells TO901317 caused a 60 % upregulation and the natural LXR agonist 22-hydroxycholesterol a 40 % upregulation of apoM. Possible causes for the differential effects in liver and intestine are discussed.
Calayir
Emine
E
Institute of Molecular Biology and Biochemistry, Ctr. for Molecular Medicine, Medical University of Graz, Austria.
Becker
Tatjana M
TM
Kratzer
Adelheid
A
Ebner
Birgit
B
Panzenböck
Ute
U
Stefujl
Jasminka
J
Kostner
Gerhard M
GM
D001053:Apolipoproteins / Q000378:metabolism*; D000075243:Apolipoproteins M; D018938:Caco-2 Cells; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D054834:Lipocalins; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D000071518:Liver X Receptors; D009928:Organ Specificity / Q000187:drug effects / Q000502:physiology; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000008:administration & dosage*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D001053:Apolipoproteins; D000075243:Apolipoproteins M; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D054834:Lipocalins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C400523:APOM protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides