Dong L M, Yamamura T, Yamamoto A
Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, Osaka, Japan.
Biochem Biophys Res Commun. 1990 Apr 30;168(2):409-14. doi: 10.1016/0006-291x(90)92336-x.
We have previously demonstrated an apolipoprotein E (apo E) mutant, apo E5, associated with hyperlipidemia and atherosclerotic vascular diseases. To investigate the possible mechanism of apo E5 involvement in the development of hyperlipidemia, we have isolated the apo E isoprotein and determined its binding activity to LDL (low density lipoprotein) receptors. It was shown that the apo E5 isoprotein was two times more active for binding to LDL receptors than apo E3. The concentration of apo E, at which 50% of 125I-labeled LDL bound to the receptor was displaced, was 29 ng/ml for apo E5 and 63 ng/ml for apo E3. This result suggests that the high affinity of apo E5 to LDL receptors results in a high uptake of apo E5-containing lipoproteins by the liver and leads to a down-regulation of LDL receptors in the liver. We can postulate that individuals with apo E5 are susceptible to hypercholesterolemia and in consequence to atherosclerosis.
我们之前已证明一种载脂蛋白E（apo E）突变体apo E5与高脂血症和动脉粥样硬化性血管疾病有关。为了研究apo E5参与高脂血症发生发展的可能机制，我们分离了apo E同工蛋白，并测定了其与低密度脂蛋白（LDL）受体的结合活性。结果显示，apo E5同工蛋白与LDL受体结合的活性是apo E3的两倍。使50%的125I标记的LDL与受体结合被取代时的apo E浓度，apo E5为29 ng/ml，apo E3为63 ng/ml。这一结果表明，apo E5对LDL受体的高亲和力导致肝脏对含apo E5的脂蛋白摄取增加，并导致肝脏中LDL受体下调。我们可以推测，携带apo E5的个体易患高胆固醇血症，进而易患动脉粥样硬化。
