ENHANCEMENT OF THE BINDING OF TRIGLYCERIDE-RICH LIPOPROTEINS TO THE VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR BY APOLIPOPROTEIN-E AND LIPOPROTEIN-LIPASE
ENHANCEMENT OF THE BINDING OF TRIGLYCERIDE-RICH LIPOPROTEINS TO THE VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR BY APOLIPOPROTEIN-E AND LIPOPROTEIN-LIPASE
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DOI：
10.1074/jbc.270.26.15747
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发表时间：
1995-06-30
影响因子：
4.8
通讯作者：
NAKAI, T
中科院分区：
文献类型：
--
作者：
TAKAHASHI, S;SUZUKI, J;NAKAI, T
低密度脂蛋白受体在胆固醇代谢中起着至关重要的作用，最近研究表明，一种与载脂蛋白E特异结合的极低密度脂蛋白受体在心脏、肌肉和脂肪组织以及人单核巨噬细胞系THP-1中表达。VLDL受体结合并内化渡边遗传性高脂血症(WHHL)兔的VLDL和中等密度脂蛋白，以及胆固醇喂养兔的β迁移性VLDL，而不是WHHL兔的低密度脂蛋白。中国仓鼠卵巢(CHO)细胞被证实能结合或内化VLDL(d<；1.006 g/ml)，但当空腹人极低密度脂蛋白与重组人载脂蛋白E(3/3)或脂蛋白脂酶(LPL)预育时，可显著增强高表达兔或人极低密度脂蛋白受体的CHO细胞的结合和内化。肝素酶处理降低了LPL介导的结合效应，但在37℃时抑制作用较低，假单胞菌LPL还在37℃增强了人空腹VLDL与VLDL受体的结合。综上所述，LPL通过脂蛋白和硫酸乙酰肝素蛋白多糖之间的桥梁及其脂解作用，使富含甘油三酯的脂蛋白与VLDL受体结合增强，Ligand印迹分析表明，VLDL受体的表观分子质量为118 kDa，小于LDL受体，这些结果表明，VLDL受体既识别也相对富含apoE的富含甘油三酯的脂蛋白，也识别分解代谢后的富含甘油三酯的脂蛋白，并通过LPL与硫酸乙酰肝素蛋白多糖相互作用，因此VLDL受体可能是肝外组织中富含甘油三酯的脂蛋白的受体。
The low density lipoprotein (LDL) receptor plays a crucial role in cholesterol metabolism, A related protein, designated the very low density lipoprotein (VLDL) receptor, that specifically binds apolipoprotein (ape) E has recently been characterized and shown to be expressed in heart, muscle and adipose tissue and the human monocyte-macrophage cell line THP-1, The VLDL receptor binds and internalizes VLDL and intermediate density lipoprotein from Watanabe heritable hyperlipidemic (WHHL) rabbits as well as beta-migrating VLDL from cholesterol-fed rabbits but not LDL from WHHL rabbits, Chinese hamster ovary (CHO) cells transfected with the rabbit VLDL receptor cDNA have now been shown to bind or internalize VLDL (d < 1.006 g/ml) isolated from fasted normolipidemic human subjects with lower affinity than WHHL-VLDL or rabbit beta-VLDL, However, binding and internalization were markedly enhanced when fasted human VLDL was preincubated with either recombinant human apoE (3/3) or lipoprotein lipase (LPL) in CHO cells overexpressing the rabbit or human VLDL receptor, CHO cells transfected with both the rabbit VLDL receptor cDNA and the human LPL cDNA effectively bound, internalized, and degraded fasted human VLDL without pretreatment. Treatment of heparinase reduced the effect of LPL-mediated binding at 4 degrees C, but the inhibitory effect was lower at 37 degrees C, Pseudomonas LPL also enhanced the binding of human fasted VLDL to the VLDL receptor at 37 degrees C in CHO cells overexpressing the human VLDL receptor, Taken together, LPL causes the enhancement of triglyceride-rich lipoproteins binding to the VLDL receptor via both the formation of bridge between lipoproteins and heparan sulfate proteoglycans and its lipolytic effect, Ligand blot analysis showed that the apparent molecular mass of the VLDL receptor is 118 kDa, which is smaller than that of the LDL receptor, These results indicate that the VLDL receptor recognizes both triglyceride-rich lipoproteins that are also relatively rich in apoE, as well as the remnants of triglyceride-rich lipoproteins after catabolism and the interaction with heparan sulfate proteoglycans by LPL, The VLDL receptor may thus function as a receptor for remnants of triglyceride-rich lipoproteins in extrahepatic tissues.