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

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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.