Carew T E, Chapman M J, Goldstein S, Steinberg D
Biochim Biophys Acta. 1978 Apr 28;529(1):171-5. doi: 10.1016/0005-2760(78)90115-7.
When 125I-labeled native low density lipoprotein was incubated with skin fibroblasts from a patient with homozygous familial hypercholesterolemia, the observed rate of degradation of the protein moiety was less than 5% the rate observed with normal fibroblasts, in agreement with previous studies. When the low density lipoprotein had been first treated with trypsin, with release of about 20% of the protein, its degradation by the patient's fibroblasts was markedly increased 8-20-fold. In contrast, the rate of degradation of the trypsin-treated lipoprotein by normal fibroblasts was, if anything, slightly reduced. In neither the normal cells nor the patient's cells was binding to the cell surface appreciably altered by trypsin treatment of the lipoprotein. Prior incubation with cholesterol and 7-ketocholesterol reduced binding of trypsin-treated low density lipoprotein to normal cells by 67% but did not affect its binding to the patient's cells. The results show that the structural modifications induced by trypsin do not interfere with binding of low density lipoprotein to its normal high affinity receptor nor its degradation by normal cells. However, the modified lipoprotein is much more readily internalized and degraded by cells from the patient with homozygous familial hypercholesterolemia.
当用¹²⁵I标记的天然低密度脂蛋白与纯合子家族性高胆固醇血症患者的皮肤成纤维细胞一起温育时，观察到蛋白质部分的降解速率不到正常成纤维细胞所观察到速率的5%，这与先前的研究一致。当低密度脂蛋白先用胰蛋白酶处理，释放出约20%的蛋白质后，患者成纤维细胞对其的降解显著增加了8至20倍。相比之下，正常成纤维细胞对经胰蛋白酶处理的脂蛋白的降解速率，即便有变化，也是略有降低。无论是正常细胞还是患者细胞，脂蛋白经胰蛋白酶处理后，其与细胞表面的结合均未明显改变。预先用胆固醇和7-酮胆固醇温育可使经胰蛋白酶处理的低密度脂蛋白与正常细胞的结合减少67%，但不影响其与患者细胞的结合。结果表明，胰蛋白酶诱导的结构修饰既不干扰低密度脂蛋白与其正常高亲和力受体的结合，也不干扰正常细胞对其的降解。然而，这种修饰后的脂蛋白更容易被纯合子家族性高胆固醇血症患者的细胞内化和降解。
