Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux.
Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux.
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DOI：
10.1194/jlr.m800362-jlr200
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发表时间：
2009-02
影响因子：
6.5
通讯作者：
Rothblat, George H.
中科院分区：
文献类型：
--
作者：
Sankaranarayanan, Sandhya;Oram, John F.;Asztalos, Bela F.;Vaughan, Ashley M.;Lund-Katz, Sissel;Adorni, Maria Pia;Phillips, Michael C.;Rothblat, George H.
关键词：
在已知的逆向胆固醇转运（RCT）机制中，ATP结合盒转运体G1 （ABCG1）介导的游离胆固醇（FC）转运是最近和研究最少的。在这里，我们利用转染人ABCG1 cDNA的幼鼠肾（BHK）细胞（经米非司酮诱导）表征了不同受体的效率。当按颗粒数和颗粒表面积归一化后，FC外排的受体效率为：小单层囊泡(SUV)>LDL>重构HDL>HDL2 = HDL3。根据磷脂含量，顺序颠倒了。ABCG1也介导磷脂外排到人血清和HDL3。abcg1介导的FC外排与25例正常血脂患者血清中HDL亚组分和成分显著相关：载脂蛋白a - ii (apoA-II) （r2 = 0.7）、载脂蛋白a - i (apoA-I) （r2 = 0.5）、HDL- c （r2 = 0.4）、HDL- pl （r2 = 0.4）、α-2 HDL （r2 = 0.4）和β前HDL （r2 = 0.2）。当细胞与放射性标记的HDL3孵育时，ABCG1不增强FC或胆固醇油基醚（COE）的内流。ABCG1表达不增加HDL3与细胞的相关性。与对照细胞相比，ABCG1的表达显著增加了可用于外排的FC池和外排速率常数。总之，组成和颗粒大小决定了abcg1介导的外排的受体效率。ABCG1增加细胞膜FC池并改变其解吸到水相的速率，而不增强与受体的结合。
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.