title: Regulated expression of endothelial lipase by porcine brain capillary endothelial cells constituting the blood-brain barrier.
abstract: Normal neurological function depends on a constant supply of polyunsaturated fatty acids to the brain. A considerable proportion of essential fatty acids originates from lipoprotein-associated lipids that undergo uptake and/or catabolism at the blood-brain barrier (BBB). This study aimed at identifying expression and regulation of endothelial lipase (EL) in brain capillary endothelial cells (BCEC), major constituents of the BBB. Our results revealed that BCEC are capable of EL synthesis and secretion. Overexpression of EL resulted in enhanced hydrolysis of extracellular high-density lipoprotein (HDL)-associated sn-2-labeled [(14)C]20 : 4 phosphatidylcholine. [(14)C]20 : 4 was recovered in cellular lipids, indicating re-uptake and intracellular re-esterification. To investigate local regulation of EL in the cerebrovasculature, BCEC were cultured in the presence of peroxisome-proliferator activated receptor (PPAR)- and liver X receptor (LXR)-agonists, known to regulate HDL levels. These experiments revealed that 24(S)OH-cholesterol (a LXR agonist), bezafibrate (a PPARalpha agonist), or pioglitazone (a PPARgamma agonist) resulted in down-regulation of EL mRNA and protein levels. Our findings implicate that EL could generate fatty acids at the BBB for transport to deeper regions of the brain as building blocks for membrane phospholipids. In addition PPAR and LXR agonists appear to contribute to HDL homeostasis at the BBB by regulating EL expression.
authors.affiliation: Institute of Molecular Biology and Biochemistry, Centre of Molecular Medicine, Medical University Graz, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sovic
authors.forename: Ute
authors.initials: U
authors.lastname: Panzenboeck
authors.forename: Andrea
authors.initials: A
authors.lastname: Wintersperger
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kratzer
authors.forename: Astrid
authors.initials: A
authors.lastname: Hammer
authors.forename: Sanja
authors.initials: S
authors.lastname: Levak-Frank
authors.forename: Sasa
authors.initials: S
authors.lastname: Frank
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.forename: Ernst
authors.initials: E
authors.lastname: Malle
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sattler
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology*; D001921:Brain / Q000201:enzymology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008049:Lipase / Q000096:biosynthesis* / Q000235:genetics; D013552:Swine
chemical_list: C410382:LIPG protein, human; D008049:Lipase