Sehayek E, Eisenberg S
Department of Medicine B, Hadassah University Hospital, Jerusalem, Israel.
J Biol Chem. 1991 Sep 25;266(27):18259-67.
The mechanism of inhibition by apolipoprotein C of the uptake and degradation of triglyceride-rich lipoproteins from human plasma via the low density lipoprotein (LDL) receptor pathway was investigated in cultured human skin fibroblasts. Very low density lipoprotein (VLDL) density subfractions and intermediate density lipoprotein (IDL) with or without added exogenous recombinant apolipoprotein E-3 were used. Total and individual (C-I, C-II, C-III-1, and C-III-2) apoC molecules effectively inhibited apoE-3-mediated cell metabolism of the lipoproteins through the LDL receptor, with apoC-I being most effective. When the incubation was carried out with different amounts of exogenous apoE-3 and exogenous apoC, it was shown that the ratio of apoE-3 to apoC determined the uptake and degradation of VLDL. Excess apoE-3 overcame, at least in part, the inhibition by apoC. ApoC, in contrast, did not affect LDL metabolism. Neither apoA-I nor apoA-II, two apoproteins that do not readily associate with VLDL, had any effect on VLDL cell metabolism. The inhibition of VLDL and IDL metabolism cannot be fully explained by interference of association of exogenous apoE-3 with or displacement of endogenous apoE from the lipoproteins. IDL is a lipoprotein that contains both apoB-100 and apoE. By using monoclonal antibodies 4G3 and 1D7, which specifically block cell interaction by apoB-100 and apoE, respectively, it was possible to assess the effects of apoC on either apoprotein. ApoC dramatically depressed the interaction of IDL with the fibroblast receptor through apoE, but had only a moderate effect on apoB-100. The study thus demonstrates that apoC inhibits predominantly the apoE-3-dependent interaction of triglyceride-rich lipoproteins with the LDL receptor in cultured fibroblasts and that the mechanism of inhibition reflects association of apoC with the lipoproteins and specific concentration-dependent effects on apoE-3 at the lipoprotein surface.
在培养的人皮肤成纤维细胞中研究了载脂蛋白C通过低密度脂蛋白（LDL）受体途径抑制富含甘油三酯的脂蛋白从人血浆中摄取和降解的机制。使用了极低密度脂蛋白（VLDL）密度亚组分以及添加或未添加外源性重组载脂蛋白E-3的中间密度脂蛋白（IDL）。总的和单个的（C-I、C-II、C-III-1和C-III-2）载脂蛋白C分子通过LDL受体有效抑制载脂蛋白E-3介导的脂蛋白细胞代谢，其中载脂蛋白C-I最有效。当用不同量的外源性载脂蛋白E-3和外源性载脂蛋白C进行孵育时，结果表明载脂蛋白E-3与载脂蛋白C的比例决定了VLDL的摄取和降解。过量的载脂蛋白E-3至少部分克服了载脂蛋白C的抑制作用。相比之下，载脂蛋白C不影响LDL代谢。载脂蛋白A-I和载脂蛋白A-II这两种不易与VLDL结合的载脂蛋白对VLDL细胞代谢均无影响。VLDL和IDL代谢的抑制不能完全用外源性载脂蛋白E-3与脂蛋白的结合干扰或内源性载脂蛋白E从脂蛋白上的置换来解释。IDL是一种同时含有载脂蛋白B-100和载脂蛋白E的脂蛋白。通过分别使用特异性阻断载脂蛋白B-100和载脂蛋白E与细胞相互作用的单克隆抗体4G3和1D7，可以评估载脂蛋白C对任一载脂蛋白的影响。载脂蛋白C显著降低了IDL通过载脂蛋白E与成纤维细胞受体的相互作用，但对载脂蛋白B-100只有中等程度的影响。因此，该研究表明，载脂蛋白C主要抑制培养的成纤维细胞中富含甘油三酯的脂蛋白与LDL受体的载脂蛋白E-3依赖性相互作用，并且抑制机制反映了载脂蛋白C与脂蛋白的结合以及在脂蛋白表面对载脂蛋白E-3的特定浓度依赖性作用。
