Mamotte C D, Sturm M, Foo J I, van Bockxmeer F M, Taylor R R
Department of Biochemistry, Royal Perth Hospital, Perth, Western Australia 6001, Australia.
Am J Physiol. 1999 Mar;276(3):E553-7. doi: 10.1152/ajpendo.1999.276.3.E553.
Compared with apolipoprotein E3 (apoE3), apoE2 is less effective in mediating the binding of lipoproteins to the low-density lipoprotein (LDL) receptor. The influence of the E4 isoform, which is associated with adverse effects on plasma lipids and coronary heart disease, is less clear. We compared the ability of very low density lipoprotein (VLDL) and LDL from paired E4/4 and E3/3 subjects to compete against 125I-labeled LDL for binding with the LDL receptor on cultured fibroblasts and Hep G2 cells. The concentrations of VLDL or LDL required to inhibit binding of 125I-LDL by 50% (IC50, microgram apoB/ml) were determined, and results were assessed in terms of an IC50 ratio, E4/4 IC50 relative to E3/3 IC50, to reduce the influence of interassay variability. In Hep G2 cells, E4/4 VLDL was more effective than E3/3 VLDL in competing for the LDL receptor, the IC50 ratio being lower than unity (0.73 +/- 0.31, P < 0.05, two-tailed t-test). IC50 values themselves were marginally lower in E4/4 than E3/3 subjects (3.7 +/- 1.3 vs. 6.1 +/- 3.7, P < 0.08). However, there was no difference between E4/4 and E3/3 VLDL in competing for the LDL receptor on fibroblasts or between E4/4 and E3/3 LDL in competing for the LDL receptor on either cell type. These results suggest that inheritance of apoE4 is associated with an increased affinity of VLDL particles for LDL receptors on hepatocytes and may partly explain the influence of the E4 isoform on lipid metabolism.
与载脂蛋白E3（apoE3）相比，apoE2在介导脂蛋白与低密度脂蛋白（LDL）受体结合方面效果较差。与血浆脂质和冠心病不良影响相关的E4异构体的影响尚不清楚。我们比较了来自配对的E4/4和E3/3受试者的极低密度脂蛋白（VLDL）和LDL与125I标记的LDL竞争结合培养的成纤维细胞和Hep G2细胞上LDL受体的能力。测定抑制125I-LDL结合50%所需的VLDL或LDL浓度（IC50，微克载脂蛋白B/毫升），并根据IC50比值（E4/4 IC50相对于E3/3 IC50）评估结果，以减少测定间变异性的影响。在Hep G2细胞中，E4/4 VLDL在竞争LDL受体方面比E3/3 VLDL更有效，IC50比值低于1（0.73±0.31，P<0.05，双侧t检验）。E4/4受试者的IC50值本身略低于E3/3受试者（3.7±1.3对6.1±3.7，P<0.08）。然而，在成纤维细胞上竞争LDL受体时，E4/4和E3/3 VLDL之间没有差异，在两种细胞类型上竞争LDL受体时，E4/4和E3/3 LDL之间也没有差异。这些结果表明，apoE4的遗传与VLDL颗粒对肝细胞上LDL受体的亲和力增加有关，这可能部分解释了E4异构体对脂质代谢的影响。
