CELLULAR AND MOLECULAR BIOLOGY OF LIPOPROTEIN METABOLISM

脂蛋白代谢的细胞和分子生物学

• 批准号: 7258972
• 负责人: Michael C. Phillips
• 金额: $ 206.23万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7258972
• 关键词: CELLULAR; MOLECULAR; BIOLOGY; LIPOPROTEIN; METABOLISM

DESCRIPTION (provided by applicant): This application represents a continuation of a Program Project whose overall theme is the metabolism of high density lipoprotein (HDL) as related to the development of atherosclerosis. The mechanisms by which HDL mediates reverse cholesterol transport (RCT), the process whereby cholesterol is removed from peripheral cells and transported to the liver for clearance from the body, will be investigated. Experiments will be conducted in a coordinated fashion at the molecular, cellular and whole animal levels. The goal is to delineate the contribution of HDL's function in RCT to the cardioprotective properties of this lipoprotein. This Program Project consists of three closely related projects: Dr. Rothblat's project involves an investigation of how the HDL receptors, scavenger receptor class B, type I and ATP-binding cassette transporter A1 (ABCA1), mediate cholesterol flux between cells and serum components. The contributions of different serum factors to the efflux of cholesterol from cells and the RCT pathway will be defined. Dr. Phillips' project proposes to elucidate the properties of the domains of apolipoprotein (apo) A-I responsible for phospholipid binding and interaction with ABCA1 and SR-BI. The molecular mechanisms by which apo A-I delivers and removes cholesterol to and from cell plasma membranes will be investigated. Dr. Rader's project focuses on the use of in vivo methods in mice to investigate the structure-function properties of apo A-I with respect to its ability to promote RCT and reduce atherosclerosis. Emphasis will be placed on acute overexpression models of apo A-I and the importance of expression of SR-BI and ABCA1 will be examined. 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 disciplines encompassed by these investigators include biochemistry, cell biology, molecular biology and animal physiology. The three specific projects are supported by three core laboratories: 1) Administrative/Central Service Core, 2) Tissue Culture Core and 3) Lipoprotein Core.

描述（由申请人提供）： 该应用代表了一个计划项目的延续，该计划项目的总体主题是与动脉粥样硬化发展相关的高密度脂蛋白（HDL）的代谢。将研究 HDL 介导反向胆固醇转运 (RCT) 的机制，即胆固醇从外周细胞中去除并转运至肝脏以从体内清除的过程。实验将以协调的方式在分子、细胞和整个动物水平上进行。目标是在 RCT 中描述 HDL 功能对该脂蛋白的心脏保护特性的贡献。该计划项目由三个密切相关的项目组成：Rothblat 博士的项目涉及研究 HDL 受体、B 类清道夫受体、I 型和 ATP 结合盒转运蛋白 A1 (ABCA1) 如何介导细胞和血清成分之间的胆固醇流动。将定义不同血清因子对细胞胆固醇流出的贡献以及 RCT 途径。 Phillips 博士的项目旨在阐明载脂蛋白 (apo) A-I 负责磷脂结合以及与 ABCA1 和 SR-BI 相互作用的结构域的特性。将研究 apo A-I 将胆固醇传递到细胞质膜和从细胞质膜去除胆固醇的分子机制。 Rader 博士的项目重点是利用小鼠体内方法来研究 apo A-I 的结构功能特性，了解其促进 RCT 和减少动脉粥样硬化的能力。 重点将放在 apo A-I 的急性过度表达模型上，并将检查 SR-BI 和 ABCA1 表达的重要性。 组成该计划项目的研究人员小组在脂质和脂蛋白代谢方面有着相似的兴趣和目标，同时提供广泛的科学专业知识。 这些研究人员涵盖的科学学科包括生物化学、细胞生物学、分子生物学和动物生理学。 这三个具体项目由三个核心实验室支持：1) 行政/中央服务核心、2) 组织培养核心和 3) 脂蛋白核心。