Apolipoproteins A-I, A-II and E are independently distributed among intracellular and newly secreted HDL of human hepatoma cells
Apolipoproteins A-I, A-II and E are independently distributed among intracellular and newly secreted HDL of human hepatoma cells
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DOI：
10.1016/j.bbalip.2009.07.004
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发表时间：
2009-12-01
影响因子：
4.8
通讯作者：
Pownall, Henry J.
中科院分区：
文献类型：
--
作者：
Gillard, Baiba K.;Lin, Hu-Yu Alice;Pownall, Henry J.
尽管肝细胞分泌主要的人血浆高密度脂蛋白（HDL）-蛋白，载脂蛋白A-I，作为无脂和脂化的物质，载脂蛋白A-II和载脂蛋白E的生物起源路线是未知的。人血浆和HepG 2细胞衍生的apo A-II和apo E以单体、同源二聚体和异源二聚体形式存在。比apo A-I更亲脂的apo A-II的二聚化由脂质表面催化。因此，我们假设细胞内和分泌的载脂蛋白A-II的脂化超过载脂蛋白AI，一旦脂化，载脂蛋白A-II二聚化。通过尺寸排阻色谱法对HepG 2细胞裂解物和培养基进行分级显示，细胞内载脂蛋白A-II和载脂蛋白E完全脂化，分别发生在新生HDL和VLDL上，而仅45%的细胞内载脂蛋白A-I脂化。载脂蛋白A-II和载脂蛋白E分别在小HDL、LDL和大HDL上分泌。含有载脂蛋白A-II和载脂蛋白A-I的HDL颗粒仅在从HepG 2和Huh 7肝癌细胞分泌后形成。载脂蛋白A-II在细胞内二聚化，而细胞内载脂蛋白E是单体，但分泌后与HDL结合，随后二聚化。因此，HDL载脂蛋白AI、A-II和E在HDL形成过程中具有不同的肝脂化和二聚化的细胞内和分泌后途径。这些早期形式的HDL预计将遵循不同的载脂蛋白特异性途径，通过血浆重塑和逆转胆固醇转运。(C)2009爱思唯尔有限公司版权所有。
Whereas hepatocytes secrete the major human plasma high density lipoproteins (HDL)-protein, apo A-I, as lipid-free and lipidated species, the biogenic itineraries of apo A-II and apo E are unknown. Human plasma and HepG2 cell-derived apo A-II and apo E occur as monomers, homodimers and heterodimers. Dimerization of apo A-II, which is more lipophilic than apo A-I, is catalyzed by lipid surfaces. Thus, we hypothesized that lipidation of intracellular and secreted apo A-II exceeds that of apo AI, and once lipidated, apo A-II dimerizes. Fractionation of HepG2 cell lysate and media by size exclusion chromatography showed that intracellular apo A-II and apo E are fully lipidated and occur on nascent HDL and VLDL respectively, while only 45% of intracellular apo A-I is lipidated. Secreted apo A-II and apo E occur on small HDL and on LDL and large HDL respectively. HDL particles containing both apo A-II and apo A-I form only after secretion from both HepG2 and Huh7 hepatoma cells. Apo A-II dimerizes intracellularly while intracellular apo E is monomeric but after secretion associates with HDL and subsequently dimerizes. Thus, HDL apolipoproteins AI, A-II and E have distinct intracellular and post-secretory pathways of hepatic lipidation and dimerization in the process of HDL formation. These early forms of HDL are expected to follow different apolipoprotein-specific pathways through plasma remodeling and reverse cholesterol transport. (C) 2009 Elsevier B.V. All rights reserved.