CELLS PROCESSING HIGH DENSITY LIPOPROTEINS

处理高密度脂蛋白的细胞

• 批准号: 2217399
• 负责人: EVE P REAVEN
• 金额: $ 11.5万
• 依托单位: VETERANS ADMIN PALO ALTO HEALTH CARE SYS
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2217399
• 关键词: CELLS; PROCESSING; DENSITY; LIPOPROTEINS

The 'selective' pathway for cellular uptake of lipoprotein-derived cholesteryl esters represents a high capacity, regulatable delivery system in which more cholesterol than apoprotein is internalized by cells. In this pathway, various cholesterol-rich lipoproteins bind to the surface of cells and cholesteryl esters are extracted without the lipoproteins entering the cells as intact particles. The 'selective' uptake of cholesterol has been shown to occur in intact steroidogenic organs, intact liver and a large variety of animal cells in culture. Yet, despite the extensive use of this pathway, we know very little about its mechanism of action, its time course, its intracellular targets, function, sites of regulation, dynamic interaction with other cholesterol-containing compartment of the cell, etc. It is the aim of this proposal to systematically study these issues using rat (and bovine?) steroidogenic and hepatic tissues. Our study is divided into 3 sections: In the first we will examine the itinerary of lipoprotein- derived cholesteryl ester transport and function in intact cell systems in which we ask whether cholesterol taken up by this pathway regulates cholesterol synthesizing enzymes, whether it is stored by the cells or used directly, how it is transported, where it is transported, to what extent it mixes with other intracellular cholesterol pools, and what regulates its amount and function. In the second section, we will use cell-free techniques to identify the various tissue factors and lipoprotein and membrane characteristics which influence 'selective' cholesterol uptake by cells. In the third section we will use cell transfection methods to modify certain intracellular proteins believed to influence the uptake and transfer of lipoprotein-cholesteryl esters during steroidogenesis. this study will combine the use of morphological, biochemical and molecular biology techniques which we believe bring a unique perspective to this field of research.

脂蛋白衍生的细胞摄取的“选择性”途径 胆固醇酯代表高容量，可调节的交付 与脂蛋白相比，胆固醇更多的系统由 细胞。 在此途径中，各种富含胆固醇的脂蛋白与 细胞和胆固醇酯的表面是提取的 脂蛋白以完整的颗粒进入细胞。 “选择性” 胆固醇的摄取已显示出在完整的类固醇中发生 器官，完整的肝脏和各种动物细胞的培养物。 然而，尽管广泛使用了这条途径，但我们对 它的作用机理，时间过程，其细胞内目标， 功能，调节部位，与其他的动态相互作用 细胞的含胆固醇隔室等。这是 该建议使用大鼠系统地研究这些问题（和 牛？）类固醇生成和肝组织。 我们的研究分为 3个部分：首先，我们将检查脂蛋白的行程 - 衍生的胆固醇酯在完整的细胞系统中的运输和功能 我们询问胆固醇是否通过这种途径进行调节 胆固醇合成酶，无论是由细胞储存还是 直接使用，如何运输，运输的位置，到什么 它与其他细胞内胆固醇池混合在一起，什么 调节其数量和功能。 在第二部分中，我们将使用 无细胞的技术来识别各种组织因素和 脂蛋白和膜特征会影响“选择性” 细胞摄入胆固醇。 在第三部分中，我们将使用单元格 转染方法修改了某些信念的细胞内蛋白 影响脂蛋白 - 色脂蛋白酯的摄取和转移 在类固醇发生期间。 这项研究将结合使用 我们的形态，生化和分子生物学技术 相信为这一研究带来独特的视角。