REGULATION OF LRP EXPRESSION AND FUNCTION IN THE CNS

CNS 中 LRP 表达和功能的调节

• 批准号: 6322053
• 负责人: ISA M HUSSAINI
• 金额: $ 5万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6322053
• 关键词: SCID mouse; astrocytes; astrocytoma; cell biology; cell line; cell migration; cytokine; epidermal growth factor; glia; growth factor receptors; immunoelectron microscopy; mitogen activated protein kinase; neoplasm /cancer invasiveness; northern blottings; nuclear factor kappa beta; nuclear runoff assay; receptor binding; receptor expression; transcription factor; western blottings

LP is an endocytic receptor involved in the trafficking of a variety of proteins/protein complexes that have physiologic relevance in the CNS including PNII, lipoprotein metabolites and activated a2M. Receptor associated protein (RAP) copurifies with LRP and blocks cell surface binding of LRP ligands. Regulation of LRP expression might have important biological roles in the nervous system. LRP is developmentally regulated in neurons. In glial cells, LRP appears to be upregulated in certain reactive states and following neoplastic transformation. The hypotheses of this proposal are that: 1) LP and RAP expression in the CNS are dynamically regulated and differentially regulated in astroglial and neuronal cell types and 2) that LRP plays a role in the control of astroglial migration/invasion. The 3 aims are to 1) demonstrate that EGFR ligands and LPS regulated the expression of LRP and RAP in neural cells 2) determine the effect of EGFR ligands and LPS on LRP promoter activity and define the transcription factors responsible for cell type-specific LRP expression in the CNS, and 3) demonstrate the role of LRP expression on neoplastic astrocyte migration/invasion.

LP 是一种内吞受体，参与多种物质的运输 与中枢神经系统具有生理相关性的蛋白质/蛋白质复合物 包括 PNII、脂蛋白代谢物和活化的 a2M。 受体 相关蛋白 (RAP) 与 LRP 共纯化并封闭细胞表面 LRP 配体的结合。 LRP 表达的调节可能具有 在神经系统中发挥重要的生物学作用。 LRP 是 神经元的发育调节。 在神经胶质细胞中，LRP 似乎 在某些反应状态和肿瘤发生后上调 转变。 该提案的假设是：1）LP 和 CNS 中的 RAP 表达是动态调节的 在星形胶质细胞和神经元细胞类型中受到差异性调节，2) LRP 在控制星形胶质细胞迁移/侵袭中发挥作用。 3号 目的是 1) 证明 EGFR 配体和 LPS 调节 2) 神经细胞中LRP和RAP表达的影响 EGFR配体和LPS对LRP启动子活性的影响并定义 负责细胞类型特异性 LRP 表达的转录因子 在 CNS 中，3) 证明 LRP 表达对 肿瘤性星形胶质细胞迁移/侵袭。