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: 7720360
• 负责人: BORIS SABIRZHANOV
• 金额: $ 2.06万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720360
• 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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 哺乳动物Tolloid-like 1(Tll-1)是Tolloid家族蛋白中的一种天冬氨酸金属蛋白酶。TLL-1可裂解BMPs的抑制因子--嗜铬蛋白，增强BMPs的活性。胎儿期应激和糖皮质激素降低了小鼠海马区TLL-1的表达，而自愿运动则增加了TLL-1基因的表达。此外，在运动期间，它已被证明增加了小鼠海马区新神经元的数量。我们发现在TLL-1启动子中存在一个潜在的缺氧诱导因子1(HIF-1)结合位点。我们假设T11-1蛋白是一个低氧反应基因。我们推测，运动中间歇性低氧增加了TLL-1的表达，并可能导致神经发生的增加。