Morton R E, Greene D J
Department of Cell Biology, Cleveland Clinic Foundation, OH 44195.
J Lipid Res. 1994 May;35(5):836-47.
Lipid transfer protein (LTP) remodels plasma lipoproteins by promoting mass transfers of cholesteryl ester (CE) and triglyceride between lipoproteins. We have investigated the capacity of an additional plasma protein, lipid transfer inhibitor protein (LTIP) to modify the functional activity of LTP in a complex mixture of lipoproteins. Transfer assays containing isolated LTP, LTIP, and the three major lipoprotein classes, and assays with intact human plasma supplemented with exogenous LTIP were used. In both assays, the inhibition of CE transfer by LTIP varied markedly depending on the lipoproteins involved and was dependent on LTIP concentration. Inhibition of lipid transfer between a given pair of lipoproteins was similar. However, between lipoprotein pairs the extent of inhibition was very different, varying up to 7-fold. Inhibition followed the order of very low density lipoprotein (VLDL)-low density lipoprotein (LDL) transfers > LDL-high density lipoprotein (HDL) transfers > VLDL-HDL transfers. Consistent with the preferential inhibition of transfer events involving LDL, LTIP was shown by gel filtration studies to associate primarily with LDL in plasma. The addition of LTIP to native plasma stimulated the LTP-mediated efflux of CE from HDL to VLDL; this occurred at the expense of LDL CE depletion. Thus, LTIP alters the pattern of lipid transfer reactions in plasma by uniquely affecting the individual transfer events mediated by LTP. By preferentially diminishing transfer events involving LDL, especially those between VLDL and LDL, LTIP enhances the ability of LTP to remove CE from HDL, and thus alters HDL metabolism.
脂质转运蛋白（LTP）通过促进胆固醇酯（CE）和甘油三酯在脂蛋白之间的大量转移来重塑血浆脂蛋白。我们研究了另一种血浆蛋白——脂质转运抑制蛋白（LTIP）在脂蛋白复杂混合物中改变LTP功能活性的能力。使用了包含分离的LTP、LTIP和三种主要脂蛋白类别的转运试验，以及添加外源性LTIP的完整人血浆试验。在这两种试验中，LTIP对CE转移的抑制作用因所涉及的脂蛋白不同而有显著差异，并且依赖于LTIP的浓度。对给定的一对脂蛋白之间脂质转移的抑制作用相似。然而，在不同的脂蛋白对之间，抑制程度差异很大，可以高达7倍。抑制作用的顺序为极低密度脂蛋白（VLDL）-低密度脂蛋白（LDL）转移＞低密度脂蛋白-高密度脂蛋白（HDL）转移＞极低密度脂蛋白-高密度脂蛋白转移。与对涉及LDL的转移事件的优先抑制一致，凝胶过滤研究表明LTIP在血浆中主要与LDL结合。向天然血浆中添加LTIP会刺激LTP介导的CE从HDL向VLDL的流出；这是以LDL中CE的消耗为代价的。因此，LTIP通过独特地影响LTP介导的个体转移事件来改变血浆中的脂质转移反应模式。通过优先减少涉及LDL的转移事件，尤其是极低密度脂蛋白和低密度脂蛋白之间的转移事件，LTIP增强了LTP从HDL中去除CE的能力，从而改变了HDL代谢。
