Pittman R C, Knecht T P, Rosenbaum M S, Taylor C A
J Biol Chem. 1987 Feb 25;262(6):2443-50.
We have previously described in rats the selective uptake of HDL-associated cholesterol esters (traced by [3H]cholesteryl oleyl ether) in excess of the uptake of HDL-associated apoA-I. In the present studies we show that the mechanism also exists in cultured cells of human and mouse origin as well. This selective uptake represents a net uptake of cholesterol esters and not an isotope exchange, as shown by mass flux studies in adrenal cells. Inhibitors of receptor recycling, chloroquine, monensin, and colchicine, inhibited uptake of apoA-I from HDL by Hep G-2 human hepatoma cells to about the same extent as a reference protein, asialofetuin, but inhibited uptake of the cholesteryl ether tracer much less. Levels of NaN3 which effectively inhibited sucrose pinocytosis inhibited uptake of apoA-I to about the same extent but did not inhibit uptake of the cholesteryl ether at all. Thus, not only receptor recycling, but endocytosis as well, appears not to be involved in selective uptake. This conclusion was supported by studies in which synthetic HDL particles were made to contain two neutral lipid core tracers; one of them, the [3H]cholesteryl ether previously used, was selectively taken up, whereas the other, [14C]sucrose octaoleate, was excluded from selective uptake. Thus, selective uptake cannot involve endocytosis of the entire lipid core, but may involve other specific transfer mechanisms.
我们之前曾在大鼠中描述过，高密度脂蛋白（HDL）相关胆固醇酯（用[3H]胆固醇油醚追踪）的选择性摄取超过了HDL相关载脂蛋白A-I的摄取。在本研究中，我们表明这种机制在人和小鼠来源的培养细胞中也存在。如肾上腺细胞中的质量通量研究所示，这种选择性摄取代表胆固醇酯的净摄取，而非同位素交换。受体再循环抑制剂氯喹、莫能菌素和秋水仙碱对Hep G-2人肝癌细胞从HDL摄取载脂蛋白A-I的抑制程度与参考蛋白去唾液酸胎球蛋白大致相同，但对胆固醇醚示踪剂的摄取抑制作用小得多。有效抑制蔗糖胞饮作用的NaN3水平对载脂蛋白A-I摄取的抑制程度大致相同，但对胆固醇醚的摄取完全没有抑制作用。因此，似乎不仅受体再循环，而且内吞作用也不参与选择性摄取。这一结论得到了以下研究的支持：在这些研究中，合成的HDL颗粒含有两种中性脂质核心示踪剂；其中一种是之前使用的[3H]胆固醇油醚，被选择性摄取，而另一种[14C]蔗糖八油酸酯则被排除在选择性摄取之外。因此，选择性摄取不可能涉及整个脂质核心的内吞作用，而可能涉及其他特定的转运机制。
