title: Liver X receptors regulate cholesterol homeostasis in oligodendrocytes.
abstract: Cholesterol synthesis and transport in oligodendrocytes are essential for optimal myelination and remyelination in pathological conditions such as multiple sclerosis. However, little is known about cholesterol homeostasis in the myelin-forming oligodendrocytes. Liver X receptors (LXRs) are nuclear oxysterol receptors that regulate genes involved in cholesterol homeostasis and may therefore play an important role in de- and remyelination. We investigated whether LXRs regulate cholesterol homeostasis in oligodendrocytes. mRNA expression of genes encoding LXR-α and LXR-β and their target genes (ABCA1, ABCG1, ABCG4, apoE, and LDLR) was detected in oligodendrocytes derived from both neonatal and adult rats using quantitative real-time PCR. The expression of LXR-β and several target genes was increased during oligodendrocyte differentiation. We further demonstrated that treatment of primary neonatal rat oligodendrocytes with the synthetic LXR agonist T0901317 induced the expression of several established LXR target genes, including ABCA1, ABCG1, apoE, and LDLR. Treatment of oligodendrocytes with T0901317 resulted in an enhanced cholesterol efflux in the presence of apolipoprotein A-I or high-density lipoprotein particles. These data show that LXRs are involved in regulating cholesterol homeostasis in oligodendrocytes.
authors.affiliation: Biomedical Research Institute, Hasselt University, and transnational University Limburg, Diepenbeek, Belgium.
authors.forename: Katherine
authors.initials: K
authors.lastname: Nelissen
authors.forename: Monique
authors.initials: M
authors.lastname: Mulder
authors.forename: Ilse
authors.initials: I
authors.lastname: Smets
authors.forename: Silke
authors.initials: S
authors.lastname: Timmermans
authors.forename: Karen
authors.initials: K
authors.lastname: Smeets
authors.forename: Marcel
authors.initials: M
authors.lastname: Ameloot
authors.forename: Jerome J A
authors.initials: JJ
authors.lastname: Hendriks
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000941:Antigens; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D005434:Flow Cytometry; D005452:Fluoresceins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D050356:Lipid Metabolism / Q000235:genetics; D008075:Lipoproteins, HDL / Q000378:metabolism; D000071518:Liver X Receptors; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D000941:Antigens; D002784:Cholesterol; D005452:Fluoresceins; D006845:Hydrocarbons, Fluorinated; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011509:Proteoglycans; D012333:RNA, Messenger; D013449:Sulfonamides; D014316:Tritium; D000099216:Chondroitin Sulfate Proteoglycan 4; C000605215:Nr1h3 protein, rat; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C085925:calcein AM