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Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood.
Journal of Lipid Research ( IF 5.0 ) Pub Date : 2020-09-09 , DOI: 10.1194/jlr.ra120000635
Ryunosuke Ohkawa 1 , Hann Low 2 , Nigora Mukhamedova 2 , Ying Fu 2 , Shao-Jui Lai 3 , Mai Sasaoka 3 , Ayuko Hara 3 , Azusa Yamazaki 3 , Takahiro Kameda 3 , Yuna Horiuchi 3 , Peter J Meikle 2 , Gerard Pernes 2 , Graeme Lancaster 2 , Michael Ditiatkovski 2 , Paul Nestel 2 , Boris Vaisman 4 , Denis Sviridov 4 , Andrew Murphy 2 , Alan T Remaley 4 , Dmitri Sviridov 5 , Minoru Tozuka 6
Affiliation  

Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBC to high-density lipoprotein (HDL), while cholesterol from low-density lipoprotein (LDL) moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBC and plasma lipoproteins was saturable, temperature-, energy- and time-dependent consistent with an active process. We did not find LDL receptor, ATP-binding cassette transporter G1 or scavenger receptor class B type 1 in RBC but found a substantial amount of ATP-binding cassette transporter A1 (ABCA1) mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apolipoprotein A-I (apoA-I) was negligible and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL or plasma. Cholesterol efflux from and cholesterol uptake by RBC from Abca1+/+ and Abca1-/- mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBC and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, Lipoprotein Lipase and Mitochondrial Translocator Protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBC remains uncertain.

中文翻译:


红细胞和脂蛋白之间的胆固醇转运有助于血液中的胆固醇代谢。



脂蛋白在胆固醇进出组织的运输中发挥着关键作用。最近的研究还表明,红细胞(RBC)的膜上携带大量游离胆固醇,在胆固醇反向转运中发挥着重要作用。然而,人们对红细胞在全身胆固醇代谢中的确切作用知之甚少。红细胞与自体血浆或分离的脂蛋白一起孵育,导致大量净胆固醇从红细胞转移到高密度脂蛋白(HDL),而来自低密度脂蛋白(LDL)的胆固醇则向相反方向转移。此外,红细胞和血浆脂蛋白之间的双向胆固醇转运是可饱和的、温度、能量和时间依赖性的,与活跃过程一致。我们在红细胞中没有发现 LDL 受体、ATP 结合盒转运蛋白 G1 或 B 型清道夫受体 1 型,但发现了大量的 ATP 结合盒转运蛋白 A1 (ABCA1) mRNA 和蛋白质。然而,从红细胞到分离的载脂蛋白 AI (apoA-I) 的特定胆固醇流出可以忽略不计,并且使用 siRNA 沉默 ABCA1 或使用钒酸盐和普罗布考抑制不会抑制流出到 apoA-I、HDL 或血浆。 Abca1 +/+Abca1 -/-小鼠的胆固醇流出和红细胞对胆固醇的摄取相似,这反对 ABCA1 在红细胞和脂蛋白之间胆固醇流动中的作用。生物信息学分析确定 ABCA7、ABCG5、脂蛋白脂肪酶和线粒体易位蛋白是可能介导胆固醇流动的候选蛋白。 总之,这些结果表明红细胞积极参与血液中的胆固醇转运,但胆固醇转运蛋白在红细胞中的作用仍不确定。
更新日期:2020-09-13
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