Cell Mutants Defective in Cholesterol Ester Formation

胆固醇酯形成有缺陷的细胞突变体

基本信息

批准号：
8139180
负责人：
Ta Yuan CHANG
金额：
$ 45.13万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-07-01 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8139180
关键词：
7,7-azocholestanol Abbreviations Acyl Coenzyme A Amino Acids Atherosclerosis Binding Proteins Biochemical Blood Caveolae Caveolins Cell membrane Cells Characteristics Chinese Hamster Chinese Hamster Ovary Cell Cholesterol Cholesterol Esters Cholesterol Homeostasis Complex Endoplasmic Reticulum Endosomes Esterification Ethylmaleimide Glycerol Goals Golgi Apparatus Grant Health Heart Diseases Hydroxymethylglutaryl-CoA reductase Immunoglobulins In Vitro Intracellular Transport Knowledge Lipids Low-Density Lipoproteins Lysosomes Mammalian Cell Mediating Membrane Mitochondria Molecular Organelles Outcomes Research Ovary Play Polyacrylamide Gel Electrophoresis Process Proteins Regulation Regulatory Element Research Risk Factors Role SCAP protein Sodium Dodecyl Sulfate-PAGE Sphingomyelins Squalene Synthetase Stearoyl-CoA Desaturase Sterol O-Acyltransferase Sterols Testing Thin Layer Chromatography Tissues Transmembrane Domain base cholesterol trafficking diacylglycerol O-acyltransferase in vitro Assay knock-down late endosome mutant non-specific lipid transfer protein novel strategies oxysterol binding protein programs receptor sterol O-acyltransferase 1 syntaxin 16 syntaxin 6 trafficking trans-Golgi Network vesicle-associated membrane protein vesicular SNARE proteins

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of this research program is to understand the molecular mechanisms involved in the regulation of intracellular cholesterol metabolism. Based on results presented in PRELIMINARY STUDIES, in the forthcoming granting period the focus will be on studying the mechanisms of cellular cholesterol trafficking and storage processes in mammalian cells. Two Specific Aims are proposed: Specific Aim 1: To test the hypothesis that the trans-Golgi network (TGN) serves as a key organelle for transporting low-density lipoprotein (LDL)-derived cholesterol from the endosomes to the plasma membrane/endoplasmic reticulum (ER). SubAim 1.1: To test the possibility that membranes containing the Syntaxin 6/Syntaxin 16/Vti1a complex play a key role in LDL-CHOL trafficking. SubAim 1.2: To test the possibility that the v-SNAREs Vamp4/Vamp3 may contribute to LDL- CHOL transport between the NPC1 compartment and the Syntaxin 6-rich compartment. SubAim 1.3: To biochemically characterize various membrane compartments associated with 3H-CHOL derived from LDL. Specific Aim 2: To examine the functional and biochemical characteristics of caveolae in the ER. SubAim 2.1: To examine the functional characteristics of the ER caveolae in intact cells and in vitro. SubAim 2.2: To examine the biochemical characteristics of the ER caveolae in intact cells and in vitro. LDL is the major cholesterol carrier in the blood. High LDL is a risk factor for atherosclerosis, which is a major cause of heart disease. The outcome of research described in the current application will bring new knowledge about the intracellular transport and storage processes of LDL-derived cholesterol, and may help develop new approaches for reducing the amount of LDL-derived cholesterol stored in tissues. PUBLIC HEALTH RELEVANCE: Low-density lipoprotein (LDL) is the major cholesterol carrier in the blood. High LDL is a risk factor for atherosclerosis, which is a major cause of heart disease. The outcome of research described in the current application will bring new knowledge about the transport and storage process of LDL-derived cholesterol, and may help develop new approaches for reducing the amount of LDL-derived cholesterol stored in tissues.

描述（由申请人提供）：该研究计划的长期目标是了解细胞内胆固醇代谢调节所涉及的分子机制。根据初步研究中提出的结果，在即将到来的授权期内，重点将是研究哺乳动物细胞中细胞胆固醇运输和储存过程的机制。提出了两个具体目标：具体目标 1：检验跨高尔基体网络 (TGN) 作为将低密度脂蛋白 (LDL) 衍生的胆固醇从内体转运到质膜/内质网的关键细胞器的假设（ER）。子目标 1.1：测试含有 Syntaxin 6/Syntaxin 16/Vti1a 复合物的膜在 LDL-CHOL 运输中发挥关键作用的可能性。子目标 1.2：测试 v-SNARE Vamp4/Vamp3 可能有助于 NPC1 区室和富含突触蛋白 6 的区室之间 LDL-CHOL 转运的可能性。子目标 1.3：对与 LDL 衍生的 3H-CHOL 相关的各种膜区室进行生化表征。具体目标 2：检查 ER 中小窝的功能和生化特征。子目标 2.1：检查完整细胞和体外内质网小窝的功能特征。子目标 2.2：检查完整细胞和体外内质网小窝的生化特征。低密度脂蛋白是血液中主要的胆固醇载体。高低密度脂蛋白是动脉粥样硬化的危险因素，而动脉粥样硬化是心脏病的主要原因。当前申请中描述的研究成果将带来有关 LDL 衍生胆固醇的细胞内运输和储存过程的新知识，并可能有助于开发减少组织中储存的 LDL 衍生胆固醇量的新方法。公共卫生相关性：低密度脂蛋白 (LDL) 是血液中的主要胆固醇载体。高低密度脂蛋白是动脉粥样硬化的危险因素，而动脉粥样硬化是心脏病的主要原因。当前申请中描述的研究成果将带来有关 LDL 衍生胆固醇运输和储存过程的新知识，并可能有助于开发减少组织中储存的 LDL 衍生胆固醇量的新方法。