Aburatani H, Matsumoto A, Kodama T, Takaku F, Fukazawa C, Itakura H
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Am J Cardiol. 1988 Jul 25;62(3):60B-65B. doi: 10.1016/s0002-9149(88)80054-7.
To study the organ-specific effect of probucol, a potent cholesterol-lowering drug, on apolipoprotein(apo)E synthesis, rabbit apoE complementary deoxyribonucleic acid (cDNA) clones were isolated and apoE messenger ribonucleic acid (mRNA) levels were determined in various tissues isolated from probucol-treated rabbits. A 0.54 kb apoE cDNA was cloned from a rabbit liver cDNA library using a synthetic oligonucleotide probe. The amino acid sequence deduced from an apoE coding region indicated 78% homology for human apoE and 63% homology for rat apoE. RNA blot analysis showed that apoE mRNA was most abundant in the liver, then in the brain and spleen. The relative amounts of apoE mRNA were determined in tissues of rabbits fed a normal diet, or high-cholesterol (1%) diet with or without probucol (1%). ApoE mRNA levels increased 2- to 4-fold in the spleen and brain after cholesterol feeding for 4 weeks and were higher by 52 to 70% in the spleen of probucol-treated rabbits than in nontreated rabbits. This induction of apoE mRNA occurs within 7 days after the initiation of probucol treatment. However, apoE mRNA levels in the liver, a major apoE-synthesizing organ, were not enhanced after probucol treatment. These results indicate that probucol induces apoE mRNA expression specifically in the spleen and may affect apoE-mediated lipoprotein metabolism, the so-called reverse cholesterol transport.
为研究强效降胆固醇药物普罗布考对载脂蛋白（apo）E合成的器官特异性作用，分离了兔apoE互补脱氧核糖核酸（cDNA）克隆，并测定了从普罗布考处理的兔分离的各种组织中apoE信使核糖核酸（mRNA）水平。使用合成寡核苷酸探针从兔肝脏cDNA文库中克隆出一个0.54 kb的apoE cDNA。从apoE编码区推导的氨基酸序列表明与人apoE的同源性为78%，与大鼠apoE的同源性为63%。RNA印迹分析表明，apoE mRNA在肝脏中最丰富，其次是在脑和脾脏中。测定了喂食正常饮食或含或不含普罗布考（1%）的高胆固醇（1%）饮食的兔组织中apoE mRNA的相对量。胆固醇喂养4周后，脾脏和脑中的apoE mRNA水平增加了2至4倍，普罗布考处理的兔脾脏中的apoE mRNA水平比未处理的兔高52%至70%。apoE mRNA的这种诱导在普罗布考治疗开始后7天内发生。然而，普罗布考治疗后，主要的apoE合成器官肝脏中的apoE mRNA水平并未升高。这些结果表明，普罗布考特异性地诱导脾脏中apoE mRNA的表达，并可能影响apoE介导的脂蛋白代谢，即所谓的胆固醇逆向转运。
