Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux.
Among the known mechanisms of reverse cholesterol transport (RCT), ATP binding cassette transporter G1 (ABCG1)-mediated free cholesterol (FC) transport is the most recent and least studied. Here, we have characterized the efficiencies of different acceptors using baby hamster kidney (BHK) cells transfected with human ABCG1 cDNA, which is inducible upon treatment with mifepristone. When normalized on particle number and particle surface area, the acceptor efficiency for FC efflux was as follows: small unilamellar vesicles (SUV)>LDL>reconstituted HDL>HDL(2) = HDL(3). Based on phospholipid content, the order was reversed. ABCG1 also mediated phospholipid efflux to human serum and HDL(3). ABCG1-mediated FC efflux correlated significantly with a number of HDL subfractions and components in serum collected from 25 normolipidemic individuals: apolipoprotein A-II (apoA-II) (r(2) = 0.7), apolipoprotein A-I (apoA-I) (r(2) = 0.5), HDL-C (r(2) = 0.4), HDL-PL (r(2) = 0.4), alpha-2 HDL (r(2) = 0.4), and prebeta HDL (r(2) = 0.2). ABCG1 did not enhance influx of FC or cholesteryl oleyl ether (COE) when cells were incubated with radiolabeled HDL(3). ABCG1 expression did not increase the association of HDL(3) with cells. Compared with control cells, ABCG1 expression significantly increased the FC pool available for efflux and the rate constant for efflux. In conclusion, composition and particle size determine the acceptor efficiency for ABCG1-mediated efflux. ABCG1 increases cell membrane FC pools and changes its rate of desorption into the aqueous phase without enhancing the association with the acceptor.
Sankaranarayanan
Sandhya
S
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Oram
John F
JF
Asztalos
Bela F
BF
Vaughan
Ashley M
AM
Lund-Katz
Sissel
S
Adorni
Maria Pia
MP
Phillips
Michael C
MC
Rothblat
George H
GH
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000378:metabolism; D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010316:Particle Size; D010743:Phospholipids / Q000378:metabolism
C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D018076:DNA, Complementary; D010743:Phospholipids; D002784:Cholesterol