MOLECULAR CLONING OF CDNA ENCODING OXIDIZED LDL RECEPTOR

描述(摘自申请者的摘要)：长期目标 这项研究的目的是开发预防癌症进展/形成的药物 人类的动脉粥样硬化病变。动脉壁中的脂质沉积 已经在动物模型中显示了与初始积累的 巨噬细胞的脂质。到目前为止的证据表明，这种类脂是 由两个巨噬细胞以氧化低密度脂蛋白(LDL)的形式表达 受体，乙酰化低密度脂蛋白受体，和一个独特的氧化型低密度脂蛋白受体。 其目的是确定将阻止脂肪摄取的化合物。 氧化低密度脂蛋白受体。 在第一阶段，建议克隆编码氧化型低密度脂蛋白的cDNAs 巨噬细胞的受体。一个小鼠巨噬细胞cDNA文库将被 在哺乳动物细胞中瞬时表达，以及受体的克隆 将通过筛选细胞表面表达的受体进行分离 结合氧化型低密度脂蛋白。为了不克隆乙酰-低密度脂蛋白受体， 约束性研究将在下列条件下进行 乙酰化低密度脂蛋白受体被阻断。 在第二阶段，氧化型低密度脂蛋白受体将在 细胞系，这条线将被用来筛选化合物文库 阻挡活动。

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.