Arimoto I, Matsumoto C, Tanaka M, Okuhira K, Saito H, Handa T
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Lipids. 1998 Aug;33(8):773-9. doi: 10.1007/s11745-998-0269-8.
Sphingomyelin (SM) and cholesterol (Chol) are major surface lipid constituents of plasma lipoproteins. We investigated the effects of SM and Chol on the plasma clearance of lipid emulsions as a model for lipoprotein particles in rats. The presence of Chol facilitated the removal of emulsion particles from plasma, whereas SM delayed particle removal. Preinjection of lactoferrin, an inhibitor of the apolipoprotein E (apoE) receptor, revealed that the differences in clearance of emulsions were due to the differences in affinity for the apoE receptor. Measurement of apolipoprotein binding suggested that the balance of apoE and apoC (apoC-II and apoC-III) bound to emulsions caused the difference in plasma clearance of emulsion particles. That is to say, SM in the emulsion surface decreased binding of apoE, which led to a longer circulation of emulsion particles in plasma. Chol, on the other hand, decreased the ratio of apoC to apoE, which may have promoted emulsion uptake through the apoE receptor. We also examined in vitro lipolysis using immobilized lipoprotein lipase (LPL) in a heparin affinity column. Lipolysis rates were significantly reduced by the incorporation of SM into the emulsion surface, but not by the incorporation of Chol, indicating that SM in the lipoprotein surface is an important lipid component regulating LPL-mediated lipolysis. Our results suggest that the presence of SM and Chol in the lipoprotein surface plays an important role in the circulation behavior and LPL-mediated lipolysis of lipid emulsions through their effect on the selectivity of plasma protein binding.
鞘磷脂（SM）和胆固醇（Chol）是血浆脂蛋白的主要表面脂质成分。我们研究了SM和Chol对脂质乳剂血浆清除率的影响，以此作为大鼠脂蛋白颗粒的模型。Chol的存在促进了乳剂颗粒从血浆中的清除，而SM则延迟了颗粒的清除。预先注射乳铁蛋白（一种载脂蛋白E（apoE）受体抑制剂）表明，乳剂清除率的差异是由于对apoE受体亲和力的差异所致。载脂蛋白结合的测量表明，结合到乳剂上的apoE和apoC（apoC-II和apoC-III）的平衡导致了乳剂颗粒血浆清除率的差异。也就是说，乳剂表面的SM降低了apoE的结合，这导致乳剂颗粒在血浆中的循环时间延长。另一方面，Chol降低了apoC与apoE的比例，这可能促进了通过apoE受体的乳剂摄取。我们还使用肝素亲和柱中的固定化脂蛋白脂肪酶（LPL）进行了体外脂解研究。将SM掺入乳剂表面可显著降低脂解速率，但掺入Chol则不会，这表明脂蛋白表面的SM是调节LPL介导的脂解的重要脂质成分。我们的结果表明，脂蛋白表面SM和Chol的存在通过影响血浆蛋白结合的选择性，在脂质乳剂的循环行为和LPL介导的脂解中发挥重要作用。
