CHOLESTEROL-PROTEIN INTERACTIONS IN BLOOD

血液中胆固醇与蛋白质的相互作用

• 批准号: 3073584
• 负责人: PHILIP L YEAGLE
• 金额: $ 5.4万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-01 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3073584
• 关键词: adenosinetriphosphatase; atherosclerosis; blood lipoprotein; cholesterol; circular dichroism; erythrocyte membrane; fluorescence; high density lipoproteins; human tissue; low density lipoprotein; nuclear magnetic resonance spectroscopy; renal medulla; retina; sarcoplasmic reticulum

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.

该应用程序的目的是研究之间的相互作用 人体红细胞膜等中的胆固醇和蛋白质 哺乳动物膜系统和人血清脂蛋白中，低 密度基蛋白（LDL）和高密度脂蛋白（HDL）。 这 预计调查将提供关于其作用的新想法 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。 具体来说，胆固醇-蛋白质相互作用可能调节 质膜 Na+K+ATP 酶的活性，从而生化 人类肥胖、高血清胆固醇水平和动脉粥样硬化之间存在联系； 人类低密度脂蛋白中的胆固醇-蛋白质相互作用可能与低密度脂蛋白中的不同 人类 HDL，这可能与这两种脂蛋白的相反作用有关 在动脉粥样硬化的发病机制中发挥作用；胆固醇蛋白 相互作用可能为优先位置提供生化基础 哺乳动物细胞质膜中的胆固醇。 将在人类红细胞中研究胆固醇-蛋白质相互作用 膜，为了比较，与 Na+K+ATP 酶的相互作用将是 在红细胞膜和酶重组体中进行了研究 肾髓质。 胆固醇-蛋白质相互作用也将在以下方面进行研究 低密度脂蛋白和高密度脂蛋白。 除了致力于仔细研究基础生物化学之外 准备和表征这些系统，六种研究方法 将采用胆固醇-蛋白质相互作用，除了其中一种之外，所有这些都是新的 应用到这个问题上。 31P 核磁共振 (NMR) 将使用磷脂和 13C 标记胆固醇的 13C NMR，如 衍生物的圆二色性（CD）和荧光 胆固醇、CD 和石蜡酸荧光（脂质探针）、相 磷脂的转变行为和 ATP 酶的酶活性。 这种多方面的方法有望提供相当完整的情况 胆固醇相对于蛋白质的行为，在这个领域几乎没有 之前已提供信息。