REGULATION OF LRP EXPRESSION AND FUNCTION IN THE CNS

CNS 中 LRP 表达和功能的调节

• 批准号: 6393790
• 负责人: ISA M HUSSAINI
• 金额: $ 10.67万
• 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 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6393790
• 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是一种涉及各种贩运的内吞受体 在中枢神经系统中具有生理相关性的蛋白质/蛋白质复合物 包括PNII，脂蛋白代谢物和激活的A2M。 受体 相关蛋白质（RAP）用LRP将细胞表面封闭 LRP配体的结合。 LRP表达的调节可能具有 神经系统中的重要生物学作用。 LRP是 在神经元中受到开发调节。 在神经胶质细胞中，LRP似乎 在某些反应状态和肿瘤之后被上调 转型。 该提议的假设是：1）LP和 中枢神经系统中的RAP表达受到动态调节，并且 在星形胶质细胞和神经元细胞类型中受到差异调节，2） LRP在控制星形胶质迁移/入侵中起作用。 3 目的是1）证明EGFR配体和LPS调节 LRP和RAP在神经细胞中的表达2）确定 EGFR配体和LPS在LRP启动子活动中，并定义 负责细胞类型特异性LRP表达的转录因子 在中枢神经系统中，3）演示了LRP表达在 肿瘤的星形胶质细胞迁移/入侵。

项目成果

H-Ras increases urokinase expression and cell invasion in genetically modified human astrocytes through Ras/Raf/MEK signaling pathway.

H-Ras 通过 Ras/Raf/MEK 信号通路增加转基因人星形胶质细胞中的尿激酶表达和细胞侵袭。

• DOI: 10.1002/glia.20667
• 发表时间: 2008
• 期刊: Glia
• 影响因子: 6.2
• 作者: Zhao,Yunge;Xiao,Aizhen;Dipierro,CharlesG;Abdel-Fattah,Rana;Amos,Samson;Redpath,GerardT;Carpenter,JoanE;Pieper,RussellO;Hussaini,IsaM
• 通讯作者: Hussaini,IsaM