Daugherty A, Thorpe S R, Lange L G, Sobel B E, Schonfeld G
J Biol Chem. 1985 Nov 25;260(27):14564-70.
beta-Very low density lipoprotein (beta-VLDL) may be a major atherogenic lipoprotein, and knowledge of the sites of its catabolism should facilitate elucidation of mechanisms important in the regulation of its plasma concentrations. In this study, catabolic sites of beta-VLDL have been delineated in normolipidemic rabbits with a novel, radioiodinated, residualizing label, 125I-dilactitol tyramine (125I-DLT). Comparative studies of beta-VLDL and low density lipoprotein catabolism were performed with 125I-DLT conjugated to each lipoprotein and with lipoproteins iodine-labeled conventionally. Conjugation did not alter size distributions or charge characteristics of lipoprotein particles. The overall processing (binding and degradation) of lipoproteins by cultured rabbit skin fibroblasts was not influenced by 125I-DLT derivatization, suggesting that attachment of the label did not influence cell receptor-lipoprotein interactions. Furthermore, although degradation products of 125I-lipoproteins leaked out of the cells and into the medium, the degradation products of 125I-DLT lipoproteins were retained by the cells. The principal catabolic site of beta-VLDL in normolipidemic rabbits was found to be the liver with 54 +/- 4% of injected 125I retained in this organ 24 h after injection of 125I-DLT-beta-VLDL. When catabolism was normalized to tissue weight, the liver and adrenals were found to be approximately equally active in the metabolism of beta-VLDL. In agreement with results of other studies with residualizing labels, the principal organ of catabolism of 125I-DLT-LDL in vivo was the liver. The adrenals were the most highly catabolizing organ when results were normalized for tissue weight. The quantitative differences observed in the tissue distributions of injected 125I-DLT-beta-VLDL and 125I-DLT-low density lipoprotein suggested that a significant proportion of beta-VLDL is removed by tissues before conversion to low density lipoprotein.
β-极低密度脂蛋白（β-VLDL）可能是主要的致动脉粥样硬化脂蛋白，了解其分解代谢部位应有助于阐明调节其血浆浓度的重要机制。在本研究中，已使用一种新型的放射性碘化残留标记物125I-二乳糖醇酪胺（125I-DLT）在血脂正常的兔中描绘出β-VLDL的分解代谢部位。使用与每种脂蛋白结合的125I-DLT以及常规碘标记的脂蛋白对β-VLDL和低密度脂蛋白的分解代谢进行了比较研究。结合并未改变脂蛋白颗粒的大小分布或电荷特征。培养的兔皮肤成纤维细胞对脂蛋白的整体处理（结合和降解）不受125I-DLT衍生化的影响，这表明标记物的附着不影响细胞受体-脂蛋白相互作用。此外，尽管125I-脂蛋白的降解产物从细胞中泄漏到培养基中，但125I-DLT脂蛋白的降解产物被细胞保留。发现在血脂正常的兔中，β-VLDL的主要分解代谢部位是肝脏，在注射125I-DLT-β-VLDL后24小时，该器官保留了54±4%的注射125I。当将分解代谢归一化至组织重量时，发现肝脏和肾上腺在β-VLDL的代谢中活性大致相同。与其他使用残留标记物的研究结果一致，体内125I-DLT-LDL的主要分解代谢器官是肝脏。当结果归一化至组织重量时，肾上腺是分解代谢最活跃的器官。注射的125I-DLT-β-VLDL和125I-DLT-低密度脂蛋白在组织分布上观察到的定量差异表明，相当一部分β-VLDL在转化为低密度脂蛋白之前被组织清除。
