Fazio S, Yao Z
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, USA.
Arterioscler Thromb Vasc Biol. 1995 May;15(5):593-600. doi: 10.1161/01.atv.15.5.593.
Synthesis and secretion of VLDL in HepG2 cells are stimulated by several lipogenic factors, including serum. We previously found that the amount of apolipoprotein (apo) E associated with large lipoproteins such as VLDL increased under conditions of stimulated lipogenesis. The present study was designed to determine if the increased apoE association with VLDL occurs intracellularly or after secretion. In addition to HepG2, we studied rat hepatoma McA-RH7777 cells for production of endogenous rat apoE and transfected human apoE3. In both hepatoma cell lines stimulation of lipogenesis and production of large apoB-containing lipoproteins by serum resulted in increased apoE association with these particles and in decreased apoE association with HDL without affecting the total apoE output. Although evidence of apoE redistribution was seen among lipoproteins in the media, the apoE newly secreted under conditions of stimulated lipogenesis mainly associated with apoB-containing lipoproteins at the expense of its association with HDL. However, this effect was not attributable to reduced HDL lipid and apoA-I mass. Finally, redistribution of apoE from HDL to apoB-containing lipoproteins was also observed intracellularly in both HepG2 and transfected McA-RH7777 cells expressing human apoE3. These data suggest that the redistribution of apoE from HDL to apoB-containing lipoproteins upon activated lipogenesis in hepatoma cells occurs intracellularly and is not attributable to a decrease in HDL production.
包括血清在内的几种生脂因子可刺激HepG2细胞中极低密度脂蛋白（VLDL）的合成与分泌。我们之前发现，在生脂作用受到刺激的条件下，与VLDL等大脂蛋白相关的载脂蛋白（apo）E的量会增加。本研究旨在确定apoE与VLDL结合增加的现象是发生在细胞内还是分泌之后。除了HepG2细胞，我们还研究了大鼠肝癌McA-RH7777细胞，以观察内源性大鼠apoE和转染的人apoE3的产生情况。在这两种肝癌细胞系中，血清刺激生脂作用以及产生含apoB的大脂蛋白，都会导致apoE与这些颗粒的结合增加，与高密度脂蛋白（HDL）的结合减少，而不影响apoE的总输出量。尽管在培养基中的脂蛋白之间可见apoE重新分布的证据，但在生脂作用受到刺激的条件下新分泌的apoE主要与含apoB的脂蛋白结合，从而减少了与HDL的结合。然而，这种效应并非归因于HDL脂质和载脂蛋白A-I含量的减少。最后，在表达人apoE3的HepG2细胞和转染的McA-RH7777细胞内也观察到了apoE从HDL向含apoB脂蛋白的重新分布。这些数据表明，肝癌细胞中在生脂作用激活后apoE从HDL向含apoB脂蛋白的重新分布发生在细胞内，且并非归因于HDL产生的减少。
