Effects of Apolipoprotein A-I on ATP-binding Cassette Transporter A1-mediated Efflux of Macrophage Phospholipid and Cholesterol

Formation of nascent high density lipoprotein particles

Lijuan Liu, Anna Bortnick, Margaret Nickel, Padmaja Dhanasekaran, Papasani V. Subbaiah, Sissel Lund-Katz, George H. Rothblat, Michael C. Phillips

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The mechanism of formation of high density lipoprotein (HDL) particles by the action of ATP-binding cassette transporter A1 (ABCA1) is not defined completely. To address this issue, we monitored efflux to apoA-I of phosphatidylcholine (PC), sphingomyelin (SM), and unesterified (free) cholesterol (FC) from J774 macrophages, in which ABCA1 is up-regulated, and investigated the nature of the particles formed. The various apoA-I/lipid particles appearing in the extracellular medium were separated by gel filtration chromatography. The presence of apoA-I in the extracellular medium led to the simultaneous formation of more than one type of poorly lipidated apoA-I-containing particle: there were 9- and 12-nm diameter particles containing ∼3:1 and 1:1 phospholipid/FC (mol/mol), respectively, which were present together with 6-nm monomeric apoA-I. Removal of the C-terminal α-helix (residues 223-243) of apoA-I reduced phospholipid and FC efflux and prevented formation of the 9- and 12-nm HDL particles; the apoA-I variant formed larger particles that eluted in the void volume. FC loading of the J774 cells also led to the formation of larger apoA-I-containing particles that were highly enriched in FC. Besides creating HDL particles, ABCA1 mediated release of larger (20-450-nm diameter) FC-rich particles that were not involved in HDL formation and that are probably membrane vesicles. These particles contained 1: 1 PC/SM in contrast to the HDL particles, which contained 2:1 PC/SM. This is consistent with lipid raft and non-raft plasma membrane domains being involved primarily in ABCA1-mediated vesicle release and nascent HDL formation, respectively.

Original languageEnglish (US)
Pages (from-to)42976-42984
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number44
DOIs
StatePublished - Oct 31 2003
Externally publishedYes

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ATP-Binding Cassette Transporters
Macrophages
Apolipoprotein A-I
HDL Lipoproteins
Phospholipids
Cholesterol
Sphingomyelins
Phosphatidylcholines
Lipids
Cell membranes
Chromatography
Gel Chromatography
Gels
Cell Membrane
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Effects of Apolipoprotein A-I on ATP-binding Cassette Transporter A1-mediated Efflux of Macrophage Phospholipid and Cholesterol : Formation of nascent high density lipoprotein particles. / Liu, Lijuan; Bortnick, Anna; Nickel, Margaret; Dhanasekaran, Padmaja; Subbaiah, Papasani V.; Lund-Katz, Sissel; Rothblat, George H.; Phillips, Michael C.

In: Journal of Biological Chemistry, Vol. 278, No. 44, 31.10.2003, p. 42976-42984.

Research output: Contribution to journalArticle

Liu, Lijuan ; Bortnick, Anna ; Nickel, Margaret ; Dhanasekaran, Padmaja ; Subbaiah, Papasani V. ; Lund-Katz, Sissel ; Rothblat, George H. ; Phillips, Michael C. / Effects of Apolipoprotein A-I on ATP-binding Cassette Transporter A1-mediated Efflux of Macrophage Phospholipid and Cholesterol : Formation of nascent high density lipoprotein particles. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 44. pp. 42976-42984.
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AU - Dhanasekaran, Padmaja

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