Sviridov D, Sasahara T, Pyle L E, Nestel P J, Fidge N H
Baker Medical Research Institute, Prahran, Australia.
Int J Biochem Cell Biol. 1997 Apr;29(4):583-8. doi: 10.1016/s1357-2725(96)00174-4.
High-density lipoprotein plays a key role in the reverse cholesterol transport pathway as well as in the delivery of cholesterol to the liver and steroidogenic tissues. Metabolism of high-density lipoprotein is determined by one of its apolipoproteins, apolipoprotein A-I; however, the identity and function of cellular protein which binds high-density lipoprotein remains unclear. The effect of antibodies against rat high-density lipoprotein binding proteins, HB1 and HB2, on high-density lipoprotein metabolism in a rat hepatoma cell line were studied. Cells were preincubated with the antibodies and 125I-labeled high-density lipoprotein binding and uptake as well as cholesterol biosynthesis and cholesterol efflux to human plasma or isolated high-density lipoprotein were studied. Both antibodies reacted specifically with HB1 and HB2 on the ligand and Western blots, but their binding was not blocked by high-density lipoprotein. Both antibodies inhibited 125I-labeled high-density lipoprotein binding to cells by 20-40%, but stimulated 125I-labeled high-density lipoprotein uptake by up to 2.5-fold. The antibodies had no effect on cholesterol efflux or on cholesterol synthesis. It is concluded that high-density lipoprotein binding proteins, HB1 and HB2, may be involved in high-density lipoprotein uptake in the liver rather than in mediating cholesterol efflux.
高密度脂蛋白在胆固醇逆向转运途径以及将胆固醇输送到肝脏和类固醇生成组织的过程中发挥着关键作用。高密度脂蛋白的代谢由其载脂蛋白之一载脂蛋白A-I决定；然而，与高密度脂蛋白结合的细胞蛋白的身份和功能仍不清楚。研究了抗大鼠高密度脂蛋白结合蛋白HB1和HB2的抗体对大鼠肝癌细胞系中高密度脂蛋白代谢的影响。细胞先用抗体预孵育，然后研究125I标记的高密度脂蛋白的结合和摄取，以及胆固醇生物合成和胆固醇向人血浆或分离的高密度脂蛋白的流出。两种抗体在配体和免疫印迹上均与HB1和HB2特异性反应，但它们的结合不受高密度脂蛋白的阻断。两种抗体均使125I标记的高密度脂蛋白与细胞的结合抑制20%-40%，但使125I标记的高密度脂蛋白摄取增加高达2.5倍。抗体对胆固醇流出或胆固醇合成没有影响。得出的结论是，高密度脂蛋白结合蛋白HB1和HB2可能参与肝脏中高密度脂蛋白的摄取，而不是介导胆固醇流出。
