Faculty Collaboration Database

Minimal lipidation of pre-beta HDL by ABCA1 results in reduced ability to interact with ABCA1. Arterioscler Thromb Vasc Biol 2007 Aug;27(8):1828-36

Date

05/19/2007

Pubmed ID

17510466

DOI

10.1161/ATVBAHA.107.142455

Scopus ID

2-s2.0-34547622807 (requires institutional sign-in at Scopus site)   109 Citations

Abstract

OBJECTIVES: The aim of this study was to determine the role of ATP binding cassette transporter A1 (ABCA1) on generation of different-sized nascent HDLs.

METHODS AND RESULTS: HEK293 cells stably-transfected with ABCA1 (HEK293-ABCA1) or non-transfected (control) cells were incubated with lipid free 125I-apoA-I for 24 hours. Incubation of apoA-I with HEK293-ABCA1 cells, but not control cells, led to the formation of heterogeneous-sized, pre-beta migrating nascent HDL subpopulations (pre-beta1 to -4) that varied in size (7.1 to 15.7 nm), lipid, and apoA-I content. Kinetic studies suggested that all subpopulations were formed simultaneously, with no evidence for a precursor-product relationship between smaller and larger-sized particles. When isolated nascent pre-beta HDLs (pre-beta1 to -4) were added back to HEK293-ABCA1 cells, their ability to bind to ABCA1 and efflux lipid was severely compromised. Heat-denaturation of pre-beta1 HDL resulted in partial recovery of ABCA1 binding, suggesting that initial interaction of apoA-I with ABCA1 results in a constrained conformation of apoA-I that decreases subsequent binding.

CONCLUSIONS: Interaction of apoA-I with ABCA1 results in the simultaneous generation of pre-beta HDLs of discrete size and chemical composition. These nascent particles are poor substrates for subsequent lipidation by ABCA1 and presumably require additional non-ABCA1-mediated lipidation for further maturation.

Author List

Mulya A, Lee JY, Gebre AK, Thomas MJ, Colvin PL, Parks JS

MESH terms used to index this publication - Major topics in bold

ATP-Binding Cassette Transporters
Apolipoprotein A-I
Atherosclerosis
Binding, Competitive
Cells, Cultured
Cholesterol Ester Transfer Proteins
Culture Media
High-Density Lipoproteins, Pre-beta
Humans
Lipoproteins, HDL
Probability
Sensitivity and Specificity
Transfection