MOLECULAR CLONING OF CDNA ENCODING OXIDIZED LDL RECEPTOR

编码氧化LDL受体的CDNA的分子克隆

• 批准号: 3502059
• 负责人: GERDA C ENDEMANN
• 金额: $ 4.82万
• 依托单位: CALIFORNIA BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1992-03-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3502059
• 关键词: antiatherogenic agent; antiserum; complementary DNA; disease /disorder model; drug design /synthesis /production; gene expression; genetic library; laboratory mouse; low density lipoprotein; macrophage; molecular cloning; oxidized lipid; radiotracer; receptor; receptor binding; synthetic peptide

DESCRIPTION (Adapted from applicant's abstract): The long term objective of this research is to develop drugs to prevent progression/formation of atherosclerotic lesions in humans. Lipid deposition in the arterial wall has been shown in animal models to involve the initial accumulation of lipid by macrophages. Evidence to date suggests that this lipid is taken up in the form of oxidized low-density lipoprotein (LDL), by two macrophage receptor, the acetyl-LDL receptor, and a distinct oxidized-LDL receptor. The intent is to identify compounds which will block lipid uptake by the oxidized-LDL receptor. During Phase I, it is proposed to clone the cDNA encoding the oxidized-LDL receptor from macrophages. A mouse macrophage cDNA library will be expressed transiently in mammalian cells, and the clone for the receptor will be isolated by screening for the cell surface expression of receptors which bind oxidized-LDL. In order not to clone the acetyl-LDL receptor, binding studies will be carried out under conditions in which the acetyl-LDL receptor is blocked. During Phase II, the oxidized-LDL receptor will be stably expressed in a cell line, and this line will be used to screen libraries of compounds for blocking activity.

描述（改编自申请人摘要）：长期目标 这项研究的目的是开发药物，以防止进展/形成 动脉粥样硬化病变。 动脉壁脂质沉积 已经在动物模型中显示， 巨噬细胞的脂质。 迄今为止的证据表明， 在氧化低密度脂蛋白（LDL）的形式，由两个巨噬细胞 受体、乙酰低密度脂蛋白受体和不同的氧化低密度脂蛋白受体。 目的是鉴定将阻断脂质摄取的化合物， 氧化LDL受体。 在第一阶段，建议克隆编码氧化LDL的cDNA， 巨噬细胞的受体。 小鼠巨噬细胞cDNA文库将在 在哺乳动物细胞中瞬时表达， 将通过筛选受体的细胞表面表达来分离 结合氧化的低密度脂蛋白 为了不克隆乙酰低密度脂蛋白受体， 结合研究将在以下条件下进行： 乙酰-LDL受体被阻断。 在第二阶段，氧化型LDL受体将稳定表达在一个细胞中。 细胞系，该细胞系将用于筛选化合物库， 封锁活动。

项目成果

CD36 is a receptor for oxidized low density lipoprotein.

• DOI: 10.1016/s0021-9258(19)50272-1
• 发表时间: 1993-06
• 期刊: The Journal of biological chemistry
• 作者: G. Endemann;L. Stanton;K. Madden;C. M. Bryant;R. T. White;A. Protter

A macrophage Fc receptor for IgG is also a receptor for oxidized low density lipoprotein.

• DOI: 10.1016/s0021-9258(18)41692-4
• 发表时间: 1992-11
• 期刊: The Journal of biological chemistry
• 作者: Lawrence W. Stanton;R. T. White;C. M. Bryant;Andrew A. Protter;G. Endemann