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Transcriptional, Translational, And Enzymatic Metabolic Regulation By L-2 Hyroxyglutarate, Garrett Brinkley
Transcriptional, Translational, And Enzymatic Metabolic Regulation By L-2 Hyroxyglutarate, Garrett Brinkley
All ETDs from UAB
Recent studies have identified elevated levels of a small metabolite, L-2 Hydroxyglutare (L-2HG), which curiously has no known metabolic roles. Renal tumors, hypoxia as well as larval development, specifically in Drosophila, all have been identified to have high levels of L-2HG. These broad categories suggest L-2HG has a physiological role. This work uncovers the impact of elevated levels of L-2HG in altering normal kidney and renal tumors. With structural similarity to α-Ketoglutarate (αKG), L-2HG acts as a competitive inhibitor to enzymes that utilize αKG as substrates or co-factors. L-2HG is known to be metabolized by L-2HG dehydrogenase (L2HGDH). Loss of …
Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert
Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert
All ETDs from UAB
Malignant gliomas are the most prevalent primary brain tumor. They are highly aggressive and lack effective treatment options. Standard therapy includes a combination of radiation, chemotherapy, and tumor resection; however, even with aggressive treatment, median patient survival remains a dismal 12 – 14 months after diagnosis. Research has focused on understanding the unique biological mechanisms involved in glioma growth and survival in an effort to design novel therapies to treat this devastating disease. In the unique environment of the brain, gliomas have developed the ability to grow and survive at the cost of the normal surrounding brain tissue. Glutamate, the …
Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu
Role Of The Cystine/Glutamate Exchanger In Glioma Cell Biology, Toyin Adeyemi Ogunrinu
All ETDs from UAB
Changes in the glioma microenvironment including oxygen (O2) levels, supply of amino acid such as L-glutamate and L-cystine and glutathione (GSH) concentrations play a critical role in glioma biology. Previous data from our laboratory and others have implicated the L-cystine/L-glutamate exchanger, system xc- in the invasion and proliferation of cancers including glioma. The central aim of this dissertation was to characterize the contribution of L-cystine uptake, GSH synthesis and L-glutamate release to migration and proliferation of glioma cells. In my first study, I examined the role of system xc- mediated L-glutamate release on glioma migration. I show that activation of …