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 tran...
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Format: | Article |
Language: | English |
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Elsevier
2009-02-01
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Series: | Journal of Lipid Research |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520414518 |
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doaj-54cfcbcf4e7544b4823a77447af6b211 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sandhya Sankaranarayanan John F. Oram Bela F. Asztalos Ashley M. Vaughan Sissel Lund-Katz Maria Pia Adorni Michael C. Phillips George H. Rothblat |
spellingShingle |
Sandhya Sankaranarayanan John F. Oram Bela F. Asztalos Ashley M. Vaughan Sissel Lund-Katz Maria Pia Adorni Michael C. Phillips George H. Rothblat Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux Journal of Lipid Research apolipoproteins ATP binding cassette transporter G1 BHK cells binding high density lipoprotein influx |
author_facet |
Sandhya Sankaranarayanan John F. Oram Bela F. Asztalos Ashley M. Vaughan Sissel Lund-Katz Maria Pia Adorni Michael C. Phillips George H. Rothblat |
author_sort |
Sandhya Sankaranarayanan |
title |
Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux |
title_short |
Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux |
title_full |
Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux |
title_fullStr |
Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux |
title_full_unstemmed |
Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux |
title_sort |
effects of acceptor composition and mechanism of abcg1-mediated cellular free cholesterol efflux |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2009-02-01 |
description |
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>HDL2 = HDL3. Based on phospholipid content, the order was reversed. ABCG1 also mediated phospholipid efflux to human serum and HDL3. 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) (r2 = 0.7), apolipoprotein A-I (apoA-I) (r2 = 0.5), HDL-C (r2 = 0.4), HDL-PL (r2 = 0.4), α-2 HDL (r2 = 0.4), and preβ HDL (r2 = 0.2). ABCG1 did not enhance influx of FC or cholesteryl oleyl ether (COE) when cells were incubated with radiolabeled HDL3. ABCG1 expression did not increase the association of HDL3 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. |
topic |
apolipoproteins ATP binding cassette transporter G1 BHK cells binding high density lipoprotein influx |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520414518 |
work_keys_str_mv |
AT sandhyasankaranarayanan effectsofacceptorcompositionandmechanismofabcg1mediatedcellularfreecholesterolefflux AT johnforam effectsofacceptorcompositionandmechanismofabcg1mediatedcellularfreecholesterolefflux AT belafasztalos effectsofacceptorcompositionandmechanismofabcg1mediatedcellularfreecholesterolefflux AT ashleymvaughan effectsofacceptorcompositionandmechanismofabcg1mediatedcellularfreecholesterolefflux AT sissellundkatz effectsofacceptorcompositionandmechanismofabcg1mediatedcellularfreecholesterolefflux AT mariapiaadorni effectsofacceptorcompositionandmechanismofabcg1mediatedcellularfreecholesterolefflux AT michaelcphillips effectsofacceptorcompositionandmechanismofabcg1mediatedcellularfreecholesterolefflux AT georgehrothblat effectsofacceptorcompositionandmechanismofabcg1mediatedcellularfreecholesterolefflux |
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1721504260806410240 |
spelling |
doaj-54cfcbcf4e7544b4823a77447af6b2112021-04-28T06:04:47ZengElsevierJournal of Lipid Research0022-22752009-02-01502275284Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol effluxSandhya Sankaranarayanan0John F. Oram1Bela F. Asztalos2Ashley M. Vaughan3Sissel Lund-Katz4Maria Pia Adorni5Michael C. Phillips6George H. Rothblat7Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Deapartment of Medicine, University of Washington, Seattle, WA; United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MADepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Deapartment of Medicine, University of Washington, Seattle, WA; United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MADepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Deapartment of Medicine, University of Washington, Seattle, WA; United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MADepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Deapartment of Medicine, University of Washington, Seattle, WA; United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MADepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Deapartment of Medicine, University of Washington, Seattle, WA; United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MADepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Deapartment of Medicine, University of Washington, Seattle, WA; United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MADepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Deapartment of Medicine, University of Washington, Seattle, WA; United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MADepartment of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Deapartment of Medicine, University of Washington, Seattle, WA; United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MAAmong 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>HDL2 = HDL3. Based on phospholipid content, the order was reversed. ABCG1 also mediated phospholipid efflux to human serum and HDL3. 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) (r2 = 0.7), apolipoprotein A-I (apoA-I) (r2 = 0.5), HDL-C (r2 = 0.4), HDL-PL (r2 = 0.4), α-2 HDL (r2 = 0.4), and preβ HDL (r2 = 0.2). ABCG1 did not enhance influx of FC or cholesteryl oleyl ether (COE) when cells were incubated with radiolabeled HDL3. ABCG1 expression did not increase the association of HDL3 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.http://www.sciencedirect.com/science/article/pii/S0022227520414518apolipoproteinsATP binding cassette transporter G1BHK cellsbindinghigh density lipoproteininflux |