ACTIVATION OF THE MAMMALIAN TOLLOID-LIKE 1 EXPRESSION BY HYPOXIA IN HUMAN NEUROB

缺氧对人类神经元中哺乳动物 Tolloid-Like 1 表达的激活

• 批准号: 7627587
• 负责人: BORIS SABIRZHANOV
• 金额: $ 1.62万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627587
• 关键词: Binding Sites; Cleaved cell; Computer Retrieval of Information on Scientific Projects Database; Exercise; Funding; Gene Expression; Genes; Glucocorticoids; Grant; Hippocampus (Brain); Human; Hypoxia; Institution; Metalloproteases; Mus; Neurons; Numbers; Protein Family; Proteins; Research; Research Personnel; Resources; Source; United States National Institutes of Health; astacin; hypoxia inducible factor 1; inhibitor/antagonist; member; neurogenesis; prenatal stress; promoter

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mammalian Tolloid-like 1 (Tll-1) is an astacin metalloprotease that is a member of the Tolloid family of proteins. Tll-1 cleaves chrodin, an inhibitor of BMPs and potentiates tha activity of the BMPs. Prenatal stress and glucocorticoids decrease Tll-1 expression whereas voluntary exercise increases Tll-1 gene expression in the mouse hippocampus. In addition, during exercise it has been shown to increase the number of new neurons within the hippocampus of mice. We identified the presence of a potential hypoxia inducible factor 1 (HIF-1) binding site in the Tll-1 promoter. We hypothesize that T11-1 protein is a hypoxia-responsive gene. We theorize that intermittent hypoxia during exercise increases Tll-1 expression and may result in increased neurogenesis.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 哺乳动物 Tolloid 样 1 (Tll-1) 是一种虾红素金属蛋白酶，属于 Tolloid 蛋白家族的成员。 Tll-1 裂解 BMP 抑制剂 Chrodin，并增强 BMP 的活性。产前应激和糖皮质激素会降低小鼠海马中 Tll-1 的表达，而自愿运动则会增加 Tll-1 基因的表达。此外，在运动过程中，它已被证明可以增加小鼠海马体内新神经元的数量。我们发现 Tll-1 启动子中存在潜在的缺氧诱导因子 1 (HIF-1) 结合位点。我们假设T11-1蛋白是一种缺氧反应基因。我们推测运动期间间歇性缺氧会增加 Tll-1 表达，并可能导致神经发生增加。