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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 哺乳动物Tolloid-like 1（Tll-1）是一种astacin金属蛋白酶，是Tolloid蛋白家族的成员。T11 -1切割BMP抑制剂chrodin并增强BMP的活性。产前应激和糖皮质激素降低Tll-1表达，而自愿运动增加Tll-1基因表达在小鼠海马。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。我们确定了一个潜在的缺氧诱导因子1（HIF-1）结合位点的Tll-1启动子的存在。我们推测T11-1蛋白是一个低氧应答基因。我们的理论是，运动过程中的间歇性缺氧增加了Tll-1的表达，并可能导致神经发生增加。

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.