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Title: Liver X receptors regulate cholesterol homeostasis in oligodendrocytes
Authors: NELISSEN, Katherine 
Mulder, Monique
SMETS, Ilse 
SMEETS, Karen 
AMELOOT, Marcel 
Issue Date: 2012
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-alpha and LXR-beta 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-beta 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.
Notes: 000297951100006, [Nelissen, Katherine; Timmermans, Silke; Ameloot, Marcel; Hendriks, Jerome J. A.] Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium. [Nelissen, Katherine; Timmermans, Silke; Ameloot, Marcel; Hendriks, Jerome J. A.] Transnat Univ Limburg, Diepenbeek, Belgium. [Mulder, Monique] Rotterdam Univ, Div Pharmacol Vasc & Metab Dis, Dept Internal Med, Rotterdam, Netherlands. [Smets, Ilse] PHL Univ Coll, Dept PHL Bio, Diepenbeek, Belgium. [Smeets, Karen] Hasselt Univ, Ctr Environm Sci, B-3590 Diepenbeek, Belgium.
Keywords: ATP-binding cassette transporters; apolipoprotein E; low-density lipoprotein receptor; qPCR;neurosciences
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ISSN: 0360-4012
e-ISSN: 1097-4547
DOI: 10.1002/jnr.22743
ISI #: 000297951100006
Category: A1
Type: Journal Contribution
Validations: ecoom 2013
Appears in Collections:Research publications

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