Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1841, Issue 1, Pages 168-179Publisher
ELSEVIER
DOI: 10.1016/j.bbalip.2013.10.019
Keywords
ABCA2; Transporter; Cholesterol; Esterification; Sphingomyelin; Ceramide
Funding
- National Institute of Neurological Disorders and Stroke [1K01NS062113-01A2]
- Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina [P30 CA138313]
- Lipidomics Core in the SC Lipidomics and Pathobiology COBRE [P20 RR017677]
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The ATP-binding cassette transporters are a large family (similar to 48 genes divided into seven families A-G) of proteins that utilize the energy of ATP-hydrolysis to pump substrates across lipid bilayers against a concentration gradient. The ABC A subfamily is comprised of 13 members and transport sterols, phospholipids and bile acids. ABCA2 is the most abundant ABC transporter in human and rodent brain with highest expression in oligodendrocytes, although it is also expressed in neurons. Several groups have studied a possible connection between ABCA2 and Alzheimer's disease as well as early atherosclerosis. ABCA2 expression levels have been associated with changes in cholesterol and sphingolipid metabolism. In this paper, we hypothesized that ABCA2 expression level may regulate esterification of plasma membrane-derived cholesterol by modulation of sphingolipid metabolism. ABCA2 overexpression in N2a neuroblastoma cells was associated with an altered bilayer distribution of the sphingolipid ceramide that inhibited acylCoA:cholesterol acyltransferase (ACAT) activity and cholesterol esterification. In contrast, depletion of endogenous ABCA2 in the rat schwannoma cell line D6P2T increased esterification of plasma membrane cholesterol following treatment with exogenous bacterial sphingomyelinase. These findings suggest that control of ABCA2 expression level may be a key locus of regulation for esterification of plasma membrane-derived cholesterol through modulation of sphingolipid metabolism. (C) 2013 Elsevier B.V. All rights reserved.
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