Journal article
LCAT synthesized by primary astrocytes esterifies cholesterol on glia-derived lipoproteins
Journal of Lipid Research, Vol.50(5), pp.885-893
2009
Abstract
Lipid trafficking in the brain is essential for the maintenance and repair of neuronal membranes, especially after neurotoxic insults. However, brain lipid metabolism is not completely understood. In plasma, LCAT catalyses the esterification of free cholesterol on circulating lipoproteins, a key step in the maturation of HDL. Brain lipoproteins are apolipoprotein E (apoE)-containing, HDL-like particles secreted initially as lipid-poor discs by glial cells. LCAT is synthesized within the brain, suggesting that it may play a key role in the maturation of these lipoproteins. Here we demonstrate that astrocytes are the primary producers of brain LCAT. This LCAT esterifies free cholesterol on nascent apoE-containing lipopoproteins secreted from glia. ApoE is the major LCAT activator in glia-conditioned media (GCM), and both the cholesterol transporter ABCA1 and apoE are required to generate glial LCAT substrate particles. LCAT deficiency leads to the appearance of abnormal ∼8 nm particles in GCM, and exogenous LCAT restores the lipoprotein particle distribution to the wild-type (WT) pattern. In vivo, complete LCAT deficiency results in a dramatic increase in apoE-HDL and reduced apolipoprotein A-I (apoA-I)-HDL in murine cerebrospinal fluid (CSF). These data show that brain LCAT esterifies cholesterol on glial-derived apoE-lipoproteins, and influences CSF apoE and apo A-I levels. Copyright © 2009 by the American Society for Biochemistry and Molecular Biology, Inc.
Details
- Title
- LCAT synthesized by primary astrocytes esterifies cholesterol on glia-derived lipoproteins
- Authors
- V Hirsch-Reinshagen (Author) - University of British Columbia, CanadaJames J Donkin (Author) - University of British Columbia, CanadaS Stukas (Author) - University of British Columbia, CanadaJ Chan (Author) - University of British Columbia, CanadaA Wilkinson (Author) - University of British Columbia, CanadaJ Fan (Author) - University of British Columbia, CanadaJ S Parks (Author) - Wake Forest University Health Sciences, United StatesJ A Kuivenhoven (Author) - Academic Medical Centre, NetherlandsD Lütjohann (Author) - Institute of Clinical Chemistry and Pharmacology, United StatesH Pritchard (Author) - University of British Columbia, CanadaC L Wellington (Author) - University of British Columbia, Canada
- Publication details
- Journal of Lipid Research, Vol.50(5), pp.885-893
- Publisher
- American Society for Biochemistry and Molecular Biology, Inc.
- Date published
- 2009
- DOI
- 10.1194/jlr.M800584-JLR200
- ISSN
- 0022-2275
- Copyright note
- Copyright © 2009 by the American Society for Biochemistry and Molecular Biology, Inc. The published version is reproduced here in accordance with the publisher's copyright policy.
- Organisation Unit
- UniSC Clinical Trials Centre; University of the Sunshine Coast, Queensland
- Language
- English
- Record Identifier
- 99451294302621
- Output Type
- Journal article
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