CELLULAR AND MOLECULAR BIOLOGY OF LIPOPROTEIN METABOLISM

本申请代表一个计划项目的延续 总的主题是研究脂蛋白的相互作用 以及随后的脂质代谢 在细胞内。 将获得的基本信息， 研究将特别与进展有关， 动脉粥样硬化斑块的消退。 的主要重点 本研究的重点是：1）脂质与 脱辅基蛋白，2）脂质的细胞摄取、代谢和释放， 3）细胞脂质代谢与 脂质/蛋白质复合物的合成和分泌。 这个程序 项目包括五个密切相关的项目： 建议研究涉及肝脏合成的过程， 大鼠血浆脂蛋白的分泌。 特别强调 被放置在肝脏甘油三酯合成和 血浆脂蛋白的分泌。 项目2是一个 继续研究胆固醇在 脂蛋白和细胞培养。 重点放在建立- 阐明胆固醇运动的机制和调节 HDL和培养细胞之间的关系。 项目3扩展了以前的工作 从脂蛋白结构的研究到脂蛋白构象的研究 为了更好地了解脱辅基蛋白， 脂蛋白中的脱辅基蛋白-脂质相互作用。 项目4将 继续和扩大以前对细胞代谢的研究， 视黄醇和视黄酯，使用组织培养细胞作为 初步实验体系。 这些研究将建立 视黄醇和视黄酯摄取之间的关系， 细胞内酯化和水解以及分泌。 项目5将重点关注细胞内游离和 酯化胆固醇，使用各种类型的细胞， 文化 重点放在参与的因素， 从细胞中沉积和清除酯化胆固醇。 的 组成本计划项目份额的一组研究人员 在脂质和脂蛋白代谢方面有相似的兴趣和目标 同时提供广泛的科学专业知识。 科学 这些研究者所涵盖的学科包括生物化学， 生理学、物理化学、细胞和分子生物学， 营养这五个科学项目得到三个核心项目的支持。 实验室：1）行政/中央服务核心，2）组织 培养物核心和3）脂蛋白核心。

This application represents a continuation of a Program Project with the overall theme to study the interaction of lipoproteins with cells and tissues, and the subsequent metabolism of lipids within cells. The basic information that will be gained from the studies will be particularly relevant to the progression and regression of the atherosclerotic plaque. The major emphasis of this research focuses on: 1) interaction of lipids with apoproteins, 2) cellular uptake, metabolism and release of lipids, and 3) relationships between cellular lipid metabolism and the synthesis and secretion of lipid/protein complexes. This Program Project consists of five closely related projects: Project 1 proposes to study the processes involved in hepatic synthesis and secretion of plasma lipoproteins in the rat. Particular emphasis is placed on the links between hepatic triglyceride synthesis and secretion of plasma lipoproteins. Project 2 represents a continuation of studies on the flux of cholesterol between lipoproteins and cells in culture. Emphasis is placed on estab- lishing the mechanism(s) and regulation of movement of cholesterol between HDL and cultures cells. Project 3 extends previous work on the structure of lipoproteins to a study on the conformations of apoproteins in order to obtain greater understanding of the apoprotein-lipid interactions in lipoproteins. Project 4 will continue and expand previous studies on the cellular metabolism of retinol and retinyl esters, using tissue culture cells as the primary experimental system. These studies will establish the relationship between retinol and retinyl ester uptake, intracellular esterification and hydrolysis, and secretion. Project 5 will focus on the intracellular metabolism of free and esterified cholesterol, using a variety of types of cells in culture. Emphasis is placed on the factors involved in the deposition and clearance of esterified cholesterol from cells. The group of investigators comprising this Program Project share similar interests and goals in lipid and lipoprotein metabolism while providing broad scientific expertise. The scientific discipline encompassed by these investigators include biochemistry, physiology, physical chemistry, cell and molecular biology and nutrition. The five scientific projects are supported by three core laboratories: 1) Administrative/Central Service Core, 2) Tissue Culture Core and 3) Lipoprotein Core.