Transcriptional profiles of receptors and transporters involved in brain cholesterol homeostasis at the blood-brain barrier: use of an in vitro model.
Brain is the most cholesterol rich organ of the whole body and recent studies suggest a role for the blood-brain barrier (BBB) in cerebral cholesterol homeostasis. Low density lipoprotein receptor (LDLR)-related receptors and ATP-binding Cassette (ABC) transporters play an important role in peripheral sterol homeostasis. The purpose of this study was to determine the mRNA expression profiles of ABC transporters (ABCA1, 2, 3, 7 and ABCG1) and low density lipoprotein receptor (LDLR)-related receptors (LDLR, vLDLR, LRP1, LRP2 and LRP8) in BBB endothelium using an in vitro co-culture model of bovine brain capillary endothelial cells (BCECs) and rat glial cells. All transcripts tested are expressed by BCECs and in capillary extract, except vLDLR. Glial cells influence ABCG1, A1, 2, 7 and LRP1 transcription, suggesting a role in cerebral lipid supply/elimination through the modulation of the expression of these transporters and receptors by these cells. Altogether, these results highlight the importance of glial input in the BBB transport phenotype for sterol homeostasis in the central nervous system, and confirm the importance of the BBB in this process.
Gosselet
Fabien
F
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique, Université d'Artois, EA 2465, IMPRT-IFR 114, Faculté Jean Perrin, Rue Jean Souvraz, SP 18 62307 Lens, France. fabien.gosselet@univ-artois.fr
Candela
Pietra
P
Sevin
Emmanuel
E
Berezowski
Vincent
V
Cecchelli
Roméo
R
Fenart
Laurence
L
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology*; D002199:Capillary Permeability; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D015870:Gene Expression; D006706:Homeostasis; D026502:LDL-Receptor Related Proteins / Q000235:genetics* / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B / Q000235:genetics; D014158:Transcription, Genetic
D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D026502:LDL-Receptor Related Proteins; D051122:Scavenger Receptors, Class B; D002784:Cholesterol