FUNCTIONAL ANALYSIS OF THE TANGIER DISEASE GENE ABC1

丹吉尔病基因 ABC1 的功能分析

• 批准号: 6402737
• 负责人: MICHAEL Leo FITZGERALD
• 金额: $ 4.94万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-23 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6402737
• 关键词: Tangier disease; adenosinetriphosphatase; apolipoproteins; cell line; cholesterol; cholesterol esters; enzyme mechanism; high density lipoproteins; immunocytochemistry; immunoprecipitation; phosphotransferases; protein kinase A; protein kinase C; protein localization; protein protein interaction; protein structure function; tissue /cell culture; transcription factor; transport proteins; western blottings; yeast two hybrid system

Cardiovascular disease is the leading cause of mortality in western societies. Increased levels of circulating high-density lipoproteins (HDL) are thought to protect against the disease state by mediating cholesterol transport out of peripheral tissues. However, the molecular mechanisms underlying this process are incompletely characterized. The recent identification of the Tangier disease gene product (ABC1), which when mutated in human causes circulating HDL to drop to undetectable levels, has provided additional molecular insight into the process of reverse cholesterol transport. This application proposes to a structure-function analysis of ABC1 in terms of its cellular localization, protein-protein molecular description of ABC1 in relation to the ability of HDL to mobilize intracellular stores of cholesterol-esters will be helpful in the development of novel therapies for cardiovascular disease.

心血管疾病是西方社会死亡的主要原因。循环高密度脂蛋白（HDL）水平的增加被认为是通过介导胆固醇从外周组织中转运出来来预防疾病状态。然而，这一过程的分子机制是不完全的特点。最近发现的坦吉尔病基因产物（ABC 1）在人体中突变时会导致循环中的高密度脂蛋白下降到无法检测的水平，这为胆固醇反向转运过程提供了额外的分子见解。本申请提出了ABC 1的结构-功能分析在其细胞定位方面，ABC 1的蛋白质-蛋白质分子描述与HDL动员细胞内胆固醇酯储存的能力将有助于开发心血管疾病的新疗法。