Ramsamy Tanya A, Boucher Jonathan, Brown Robert J, Yao Zemin, Sparks Daniel L
Lipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, ON, Canada.
J Lipid Res. 2003 Apr;44(4):733-41. doi: 10.1194/jlr.M200339-JLR200. Epub 2003 Jan 16.
We have previously shown that hepatic lipase (HL) is inactive when bound to purified heparan sulfate proteoglycans and can be liberated by HDL and apolipoprotein A-I (apoA-I), but not by LDL or VLDL. In this study, we show that HDL is also able to displace HL directly from the surface of the hepatoma cell line, HepG2, and Chinese hamster ovary cells stably overexpressing human HL. ApoA-I is more efficient at displacing cell surface HL than is HDL, and different HDL classes vary in their ability to displace HL from the cell surface. HDL2s have a greater capacity to remove HL from the cell surface and intracellular compartments, as compared with the smaller HDL particles. The different HDL subclasses also uniquely affect the activity of the enzyme. HDL2 stimulates HL-mediated hydrolysis of VLDL-triacylglycerol, while HDL3 is inhibitory. Inhibition of VLDL hydrolysis appears to result from a decreased interlipoprotein shuttling of HL between VLDL and the smaller, more dense HDL particles. This study suggests that high HDL2 levels are positively related to efficient triacylglycerol hydrolysis by their ability to enhance the liberation of HL into the plasma compartment and by a direct stimulation of VLDL-triacylglycerol hydrolysis.
我们之前已经表明，肝脂酶（HL）与纯化的硫酸乙酰肝素蛋白聚糖结合时无活性，可被高密度脂蛋白（HDL）和载脂蛋白A-I（apoA-I）释放，但不能被低密度脂蛋白（LDL）或极低密度脂蛋白（VLDL）释放。在本研究中，我们表明HDL还能够直接从肝癌细胞系HepG2和稳定过表达人HL的中国仓鼠卵巢细胞表面置换HL。与HDL相比，apoA-I在置换细胞表面HL方面更有效，并且不同类型的HDL在从细胞表面置换HL的能力上有所不同。与较小的HDL颗粒相比，HDL2s从细胞表面和细胞内区室去除HL的能力更强。不同的HDL亚类对该酶的活性也有独特影响。HDL2刺激HL介导的VLDL-三酰甘油水解，而HDL3具有抑制作用。VLDL水解的抑制似乎是由于HL在VLDL与较小、密度更高的HDL颗粒之间脂蛋白间穿梭减少所致。本研究表明，高HDL2水平通过增强HL释放到血浆区室的能力以及直接刺激VLDL-三酰甘油水解，与有效的三酰甘油水解呈正相关。
