Young S G, Peralta F P, Dubois B W, Curtiss L K, Boyles J K, Witztum J L
Cardiology Division, San Diego Veterans Administration Hospital, La Jolla, California.
J Biol Chem. 1987 Dec 5;262(34):16604-11.
In 1979, Steinberg and colleagues described a unique kindred with familial hypobetalipoproteinemia (Steinberg, D., Grundy, S. M., Mok, H. Y. I., Turner, J. D., Weinstein, D. B., Brown, W. V., and Albers, J. J. (1979) J. Clin. Invest. 64, 292-301). Recently, we demonstrated the existence of an abnormal species of apolipoprotein (apo-) B, apo-B37 (Mr = 203,000) in nine members of that kindred (Young, S. G., Bertics, S. J., Curtiss, L. K., and Witztum, J. L. (1987) J. Clin. Invest. 79, 1831-1841; Young, S. G., Bertics, S. J., Curtiss, L. K., Dubois, B. W., and Witztum, J. L. (1987) J. Clin. Invest. 79, 1842-1851). Apolipoprotein B37 contains only the amino-terminal portion of apo-B100. In affected individuals most of the apo-B37 is contained in the high density lipoprotein (HDL) fraction (d = 1.063-1.21 g/ml), where it is the principal apolipoprotein in a unique lipoprotein (Lp) particle, Lp-B37, which contains little, if any, apo-A-I. However, the most abundant lipoprotein in the HDL density fraction is a smaller particle, which contains apo-A-I, but no apo-B. The Lp-B37 particles were isolated from the HDL of affected individuals by immunoabsorption of apo-B37. Selected affinity antibodies specific for apo-B37 were used to prepare an anti-apo-B37-Sepharose 4B column. Lipoproteins not bound by the column (unbound HDL fraction) contained apo-A-I, but no apo-B. The Lp-B37, which was eluted from the column with 3 M KI, contained apo-B37 and trace amounts of apo-A-I, but no apo-B100. Over a 4-h period, normal human fibroblasts degraded 10-fold more 125I-low density lipoprotein (LDL) than 125I-Lp-B37. Also, whereas addition of excess unlabeled LDL markedly reduced degradation of 125I-LDL, it did not significantly reduce the degradation of 125I-Lp-B37. Unlabeled Lp-B37 did not inhibit uptake and degradation of 125I-LDL by fibroblasts. These data suggest that the amino-terminal portion of apo-B100, when expressed on a naturally occurring lipoprotein particle, does not contain a functional apo-B,E(LDL) receptor binding domain.
1979年，斯坦伯格及其同事描述了一个患有家族性低β脂蛋白血症的独特家系（斯坦伯格，D.，格伦迪，S. M.，莫克，H. Y. I.，特纳，J. D.，温斯坦，D. B.，布朗，W. V.，以及阿尔伯斯，J. J.（1979年）《临床研究杂志》64卷，292 - 301页）。最近，我们在该家系的9名成员中证实了一种异常的载脂蛋白（apo-）B，即apo-B37（相对分子质量 = 203,000）的存在（扬，S. G.，贝蒂克斯，S. J.，柯蒂斯，L. K.，以及维茨图姆，J. L.（1987年）《临床研究杂志》79卷，1831 - 1841页；扬，S. G.，贝蒂克斯，S. J.，柯蒂斯，L. K.，杜波依斯，B. W.，以及维茨图姆，J. L.（1987年）《临床研究杂志》79卷，1842 - 1851页）。载脂蛋白B37仅包含apo-B100的氨基末端部分。在患病个体中，大部分的apo-B37存在于高密度脂蛋白（HDL）组分（密度d = 1.063 - 1.21 g/ml）中，在那里它是一种独特的脂蛋白（Lp）颗粒即Lp-B37中的主要载脂蛋白，Lp-B37几乎不含有（如果有的话）apo-A-I。然而，HDL密度组分中最丰富的脂蛋白是一种较小的颗粒，它含有apo-A-I，但不含apo-B。通过apo-B37的免疫吸附从患病个体的HDL中分离出Lp-B37颗粒。使用对apo-B37特异的选定亲和抗体来制备抗apo-B37 - 琼脂糖4B柱。未被该柱结合的脂蛋白（未结合的HDL组分）含有apo-A-I，但不含apo-B。用3 M KI从柱上洗脱下来的Lp-B37含有apo-B37和微量的apo-A-I，但不含apo-B100。在4小时的时间段内，正常人成纤维细胞对125I - 低密度脂蛋白（LDL）的降解量比对125I - Lp-B37的降解量多10倍。此外，虽然添加过量未标记的LDL显著降低了125I - LDL的降解，但它并未显著降低125I - Lp-B37的降解。未标记的Lp-B37不抑制成纤维细胞对125I - LDL的摄取和降解。这些数据表明，当apo-B100的氨基末端部分在天然存在的脂蛋白颗粒上表达时，它不包含功能性的apo-B,E（LDL）受体结合结构域。
