Morita Shin-ya, Kawabe Misa, Nakano Minoru, Handa Tetsurou
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Chem Phys Lipids. 2003 Nov;126(1):39-48. doi: 10.1016/s0009-3084(03)00090-2.
The chylomicron assembly has been proposed to involve the core expansion of apolipoprotein B (apoB)-containing primordial lipoproteins by fusing with triglyceride-rich lipid droplets. We examined the effects of an inhibitor of chylomicron secretion, Pluronic L81, on triolein-phosphatidylcholine emulsions and low density lipoproteins (LDL) which were used for the models of lipid droplets and primordial lipoproteins, respectively. We showed by dynamic light scattering that the sizes of lipid emulsions and LDL were increased in the presence of Pluronic L81. The binding of apoB-100 to lipid emulsions was enhanced by Pluronic L81. CD and fluorescence lifetime measurements revealed that Pluronic L81 altered the secondary structure of apoB-100 with an increased local hydration. The proper hydrophilic-to-hydrophobic balance of Pluronic L81 is important for these actions. It is proposed that Pluronic L81 inhibits the secretion of chylomicrons by leading the excess core expansion of the primordial lipoproteins and the conformational modification of apoB.
有人提出,乳糜微粒的组装过程包括通过与富含甘油三酯的脂滴融合,使含载脂蛋白B(apoB)的原始脂蛋白的核心膨胀。我们研究了乳糜微粒分泌抑制剂普朗尼克L81分别对用于模拟脂滴和原始脂蛋白的三油酸甘油酯 - 磷脂酰胆碱乳液和低密度脂蛋白(LDL)的影响。通过动态光散射我们发现,在普朗尼克L81存在的情况下,脂质乳液和LDL的尺寸增大。普朗尼克L81增强了apoB - 100与脂质乳液的结合。圆二色光谱(CD)和荧光寿命测量表明,普朗尼克L81改变了apoB - 100的二级结构,局部水合作用增加。普朗尼克L81合适的亲水 - 疏水平衡对这些作用很重要。有人提出,普朗尼克L81通过导致原始脂蛋白的过度核心膨胀和apoB的构象修饰来抑制乳糜微粒的分泌。