Rumsey S C, Obunike J C, Arad Y, Deckelbaum R J, Goldberg I J
Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York 10032.
J Clin Invest. 1992 Oct;90(4):1504-12. doi: 10.1172/JCI116018.
Lipoprotein lipase (LPL), the rate limiting enzyme for hydrolysis of lipoprotein triglyceride, also mediates nonenzymatic interactions between lipoproteins and heparan sulfate proteoglycans. To determine whether cell surface LPL increases LDL binding to cells, bovine milk LPL was added to upregulated and nonupregulated human fibroblasts along with media containing LDL. LDL binding to cells was increased 2-10-fold, in a dose-dependent manner, by the addition of 0.5-10 micrograms/ml of LPL. The amount of LDL bound to the cells in the presence of LPL far exceeded the capacity for LDL binding via the LDL receptor. Treatment of fibroblasts with heparinase and heparitinase resulted in a 64% decrease in LPL-mediated LDL binding. Compared to studies performed without LPL, more LDL was internalized and degraded in the presence of LPL, but the time course was slower than that of classical lipoprotein receptor mediated pathways. In LDL receptor negative fibroblasts, LPL increased surface bound LDL > 140-fold, intracellular LDL > 40-fold, and LDL degradation > 6-fold. These effects were almost completely inhibited by heparin and anti-LPL monoclonal antibody. LPL also increased the binding and uptake by fibroblasts of apolipoprotein-free triglyceride emulsions; binding was increased > 8-fold and cellular uptake was increased > 40-fold with LPL. LPL increased LDL binding to THP-1 monocytes, and increased LDL uptake (4.5-fold) and LDL degradation (2.5-fold) by THP-1 macrophages. In the absence of added LPL, heparin and anti-LPL monoclonal antibodies decreased LDL degradation by > 40%, and triglyceride emulsion uptake by > 50%, suggesting that endogenously produced LPL mediated lipid particle uptake and degradation. We conclude that LPL increases lipid and lipoprotein uptake by cells via a pathway not involving the LDL receptor. This pathway may be important for lipid accumulation in LPL synthesizing cells.
脂蛋白脂肪酶（LPL）是脂蛋白甘油三酯水解的限速酶，它还介导脂蛋白与硫酸乙酰肝素蛋白聚糖之间的非酶相互作用。为了确定细胞表面的LPL是否会增加低密度脂蛋白（LDL）与细胞的结合，将牛乳LPL与含有LDL的培养基一起添加到上调和未上调的人成纤维细胞中。添加0.5 - 10微克/毫升的LPL后，LDL与细胞的结合以剂量依赖的方式增加了2 - 10倍。在LPL存在的情况下，与细胞结合的LDL量远远超过通过LDL受体结合LDL的能力。用肝素酶和类肝素酶处理成纤维细胞导致LPL介导的LDL结合减少64%。与未添加LPL的研究相比，在LPL存在的情况下，更多的LDL被内化和降解，但时间进程比经典的脂蛋白受体介导途径要慢。在LDL受体阴性的成纤维细胞中，LPL使表面结合的LDL增加>140倍，细胞内LDL增加>40倍，LDL降解增加>6倍。这些作用几乎完全被肝素和抗LPL单克隆抗体抑制。LPL还增加了无载脂蛋白甘油三酯乳剂与成纤维细胞的结合和摄取；有LPL时，结合增加>8倍，细胞摄取增加>40倍。LPL增加了LDL与THP - 1单核细胞的结合，并增加了THP - 1巨噬细胞对LDL的摄取（4.5倍）和LDL降解（2.5倍）。在未添加LPL的情况下，肝素和抗LPL单克隆抗体使LDL降解减少>40%，甘油三酯乳剂摄取减少>50%，这表明内源性产生的LPL介导脂质颗粒的摄取和降解。我们得出结论，LPL通过不涉及LDL受体的途径增加细胞对脂质和脂蛋白的摄取。该途径可能对LPL合成细胞中的脂质积累很重要。
