oxalylglycine and Pheochromocytoma

Cells respond to reduced oxygen availability predominately by activation of the hypoxia-inducible factor (HIF) pathway. HIF activation upregulates hundreds of genes that help cells survive in the reduced oxygen environment. The aim of this study is to determine whether chemical-induced HIF accumulation mimics all aspects of the hypoxic response of cells. We compared the effects of dimethyloxalylglycine (DMOG) (a HIF stabiliser) on PC12 cells cultured in air oxygen (20.9% O

Topics: Adrenal Gland Neoplasms; Amino Acids, Dicarboxylic; Animals; Cell Hypoxia; Hypoxia; Nerve Growth Factor; Oxygen; PC12 Cells; Pheochromocytoma; Rats; Reactive Oxygen Species

Mitochondrial disorders arise from defects in nuclear genes encoding enzymes of oxidative metabolism. Mutations of metabolic enzymes in somatic tissues can cause cancers due to oncometabolite accumulation. Paraganglioma and pheochromocytoma are examples, whose etiology and therapy are complicated by the absence of representative cell lines or animal models. These tumors can be driven by loss of the tricarboxylic acid cycle enzyme succinate dehydrogenase. We exploit the relationship between succinate accumulation, hypoxic signaling, egg-laying behavior, and morphology in C. elegans to create genetic and pharmacological models of succinate dehydrogenase loss disorders. With optimization, these models may enable future high-throughput screening efforts.

Topics: Adrenal Gland Neoplasms; Amino Acids, Dicarboxylic; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Hypoxia; Disease Models, Animal; Drug Screening Assays, Antitumor; High-Throughput Screening Assays; Humans; Mutation; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase; Succinic Acid