CELL PROCESSING HIGH DENSITY LIPOPROTEINS

细胞处理高密度脂蛋白

• 批准号: 6684166
• 负责人: Salman Azhar
• 金额: $ 22.32万
• 依托单位: PALO ALTO VETERANS INSTIT FOR RESEARCH
• 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 2006-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6684166
• 关键词: blood lipoprotein metabolism; blood lipoprotein transport; caveolins; cell component structure /function; cell free system; cell membrane; cholesterol; cholesterol esters; corpus luteum; cytoplasm; genetic manipulation; granulosa cell; high density lipoproteins; immature animal; immunoprecipitation; laboratory mouse; laboratory rabbit; laboratory rat; protein localization; protein protein interaction; protein structure function; sphingomyelins; steroid biosynthesis; tissue /cell culture

DESCRIPTION: This proposal represents an effort to identify proteins or factors, which may be linked with the HDL receptor (scavenger receptor subtype BI, SR-BI) to facilitate the uptake of lipoprotein-donated cholesteryl esters through the unique selective cholesterol uptake pathway. This is a pathway in which circulating (i.e., exogenous) lipoproteins are able to contribute bulk cholesterol to many types of cells for synthetic purposes. Recent studies indicate that cystolic extracts from selective pathway-competent rodent steriodogenic tissues (such as luteinized ovary) enhance selective uptake in purified SR-BI-containing proteoliposomes by 8-10 fold. The proposed studies will capitalize on this finding and attempt to identify and purify the active agents in luteal tissue using a sensitive cell-free membrane reconstitution system. Potentially important known factors associated with molecular transport machinery (SNARES, sphingomyelin, caveolin etc.), will also be tested by the membrane reconstitution system using selective cholesteryl ester transport as an assay, or may be tested in cell systems containing sufficient quantities of SR-BI, but overexpressing (or lacking) certain other proteins. The idea that caveolin may be a negative regulator for SR-BI function in the selected cholesteryl ester uptake process will be thoroughly investigated, as will the idea that specialized domains of microvillar channel membranes (membrane rafts) in stereridogenic tissues represent distinct regions of the microvillar compartment specialized for efficient uptake of neutral lipids. All tissue/cell models described are available in this laboratory. Currently used technologies permit us to faithfully track proteins both biochemically and morphologically, and the integrated system we propose to study should yield detailed information on potential protein links between the SR-BI receptor and the selective uptake of lipoprotein-donated cholesterol.

描述：该建议代表识别蛋白质或 因素，可能与HDL受体有关（清道夫受体亚型） BI，SR-BI），以促进含脂蛋白含蛋白的胆固醇酯的吸收 通过独特的选择性胆固醇吸收途径。这是一条途径 哪种循环（即外源）脂蛋白能够贡献大量 用于合成目的的许多类型细胞的胆固醇。 最近的研究表明，来自选择性途径的cystolic提取物 啮齿动物的静脉组织（例如叶酸卵巢）增强选择性 在纯化的含SR-BI的蛋白脂质体中摄取8-10倍。提议 研究将利用这一发现，并试图识别和净化 使用无敏感细胞膜的黄体组织中的活性剂 重建系统。与 也将 通过膜重建系统测试使用选择性胆汁块 酯传输作为测定法，或者可以在包含的细胞系统中进行测试 足够数量的SR-BI，但过表达（或缺乏）某些其他 蛋白质。小窝蛋白可能是SR-BI功能的负调节剂的想法 在选定的胆固醇酯摄取过程中 研究了微伏通道的专业领域的想法 酯组织中的膜（膜筏）代表不同的区域 微型隔间专门用于有效摄取中性 脂质。 该实验室中所述的所有组织/细胞模型都可以使用。现在 使用的技术使我们能够忠实地在生化和 形态学上，我们建议研究的综合系统应产生 有关SR-BI受体和潜在蛋白质联系的详细信息 含脂蛋白的胆固醇的选择性摄取。