CHOLESTEROL-PROTEIN INTERACTIONS IN BLOOD

此应用程序的目的是调查以下各项之间的交互 人红细胞膜和其他组织中的胆固醇和蛋白质 哺乳动物的膜系统，以及在人类血清中的低脂蛋白 密度脂蛋白(LDL)和高密度脂蛋白(HDL)。这 预计调查将提供有关以下方面的新想法 胆固醇在动脉粥样硬化发病机制和正常哺乳动物中的作用 细胞生长。具体地说，胆固醇-蛋白质的相互作用可能会调节 质膜Na-K-ATPase的活性，从而在生化上 将人类肥胖、高血清胆固醇水平和动脉粥样硬化联系起来； 人低密度脂蛋白中胆固醇与蛋白质的相互作用可能与低密度脂蛋白不同 人类高密度脂蛋白，可能与这两种脂蛋白的相反作用有关 胆固醇蛋白在动脉粥样硬化发病机制中的作用 相互作用可能为优势位置提供生化基础。 哺乳动物细胞质膜中胆固醇的含量。 胆固醇与蛋白质的相互作用将在人类红细胞中进行研究。 为了比较，与Na K ATPase的相互作用将是 在红细胞膜和重组人红细胞膜中的研究 肾髓质。还将研究胆酯与蛋白质的相互作用。 低密度脂蛋白和高密度脂蛋白。除了基础生物化学外，还致力于 准备和表征这些系统，研究的六种方法 将使用胆固醇-蛋白质相互作用，除了一个之外，所有这些都是新的 适用于这个问题。~(31)P核磁共振谱 将使用13C标记的胆固醇的磷脂和13C核磁共振，作为 Will圆二色谱(CD)及其衍生物的荧光性质 胆固醇、镉和脂类探针巴比酸的荧光相 磷脂的过渡行为和ATPase的酶活性。 这一多方面的方法有望提供一个相当完整的图景 胆固醇相对于蛋白质的行为，在这个领域几乎没有 信息之前是可以获得的。

The purpose of this application is to investigate interactions between cholesterol and proteins in the human erythrocyte membrane and other mammalian membrane systems, and in the human serum lipoproteins, low density kipoprotein (LDL) and high density lipoprotein (HDL). This investigation is anticipated to provide new ideas concerning the role of cholesterol in the pathogenesis of atherosclerosis and in normal mammalian cell growth. Specifically, cholesterol-protein interactions may modulate the activity of the plasma membrane Na+K+ATPase, thereby biochemically linking human obesity, high serum cholesterol levels and atherosclerosis; cholesterol-protein interactions are likely different in human LDL than in human HDL, which may relate to the opposite roles these two lipoproteins play in the pathogenesis of atherosclerosis; cholesterol-protein interactions may provide a biochemical basis for the preferential location of cholesterol in the plasma membrane of mammalian cells. Cholesterol-protein interactions will be studied in the human erythrocyte membrane and for comparison, interactions with the Na+K+ATPase will be studied in the erythrocyte membranes and in recombinants of enzyme from kidney medulla. Cholesteral-protein interactions will also be studied in LDL and HDL. In addtiion to the basic biochemistry devoted to carefully preparing and characterizing these systems, six approaches to studying cholesterol-protein interactions will be employed, all but one of them new in application to this question. 31P nuclear magnetic resonance (NMR) of the phospholipids and 13C NMR of 13C labelled cholesterol will be used, as will circular dichroism (CD) and fluorescence of a derivative of cholesterol, CD and fluorescence of parinaric acid, a lipid probe, phase transition behavior of phospholipids, and enzyme activity of the ATPases. This multifaceted approach is expected to provide a rather complete picture of cholesterol behavior with respect to protein, in a field where almost no information was available previously.