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This page provides a simple browsing interface for finding entities described by a property and a named value. Other available search interfaces include the page property search, and the ask query builder.

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Property "Has-20abstract" (as page type) with input value "Succinate-20is-20a-20substrate-20mainly-20metabolized-20to-20fumarate-20in-20mitochondria-20by-20succinate-20dehydrogenase-20(SDH)-20or-20Complex-20II.-20SDH-20is-20located-20at-20the-20inner-20mitochondrial-20membrane,-20coupling-20the-20oxidation-20of-20succinate-20to-20fumarate-20in-20the-20tricarboxylic-20acid-20cycle-20(TCA)-20with-20electron-20transfer-20to-20ubiquinone.-20Inhibition-20or-20downregulation-20of-20SDH-20leads-20to-20an-20impairment-20of-20TCA-20cycle-20and-20respiratory-20activity,-20and-20consequently-20to-20accumulation-20of-20succinate.-20This,-20in-20turn,-20transmits-20an-20oncogenic-20signal-20from-20mitochondria-20to-20the-20cytosol.-20Cytosolic-20succinate-20inhibits-20the-20hypoxia-20inducible-20factor-201α-20(HIF1α)-20prolyl-20hydroxylase-20(PHD)-20leading-20to-20HIF1α-20stabilization.-20In-20this-20“pseudohypoxic”-20state-20angiogenesis-20and-20anaerobic-20metabolism-20are-20enhanced,-20ultimately-20leading-20to-20tumour-20progression.-20-0A-0AWhile-20succinate-20has-20essential-20implications-20on-20prostate-20cancer-20development,-20it-20is-20difficult-20to-20control-20intracellular-20succinate-20concentrations-20in-20intact-20cells-20due-20to-20the-20low-20permeability-20of-20plasma-20membranes-20to-20the-20compound.-20To-20overcome-20this-20limitation,-20we-20applied-20novel-20plasma-20membrane-2Dpermeable-20succinate-20(NV118)-20and-20malonate-20(inhibitor-20of-20SDH,-20NV161)-20prodrugs-20in-20high-2Dresolution-20respirometry-20(Oroboros-20O2k-2DFluoRespirometer).-20Mitochondrial-20respiration-20was-20assessed-20in-20three-20cell-20lines:-20RWPE-2D1-20(prostate-3B-20noncancerous),-20LNCaP-20(prostate-3B-20cancer),-20and-20HEK293T-20(embryonic-20kidney-3B-20control).-20-0A-0ANV118-20(250-20µM)-20stimulated-20ROUTINE-20respiration-20in-20LNCaP-20cancer-20cells-20by-2018-25-20as-20compared-20to-20vehicle-20(DMSO),-20while-20respiration-20remained-20unchanged-20in-20RWPE-2D1-20(4-25-20increase)-20and-20HEK-20293T-20cells,-20even-20at-20higher-20concentrations-20of-20the-20prodrug.-20NV161-20(66-20µM)-20had-20no-20effect-20on-20ROUTINE-20respiration-20of-20HEK-20293T-20cells.-0A-0AOur-20results-20indicate-20enhanced-20utilization-20of-20external,-20plasma-20membrane-2Dpermeable-20succinate-20in-20mitochondrial-20respiration-20in-20LNCaP-20prostate-20cancer-20cells-20but-20not-20in-20control-20cell-20lines.-20The-20cell-2Dpermeable-20prodrugs-20offer-20promising-20research-20tools-20to-20elucidate-20the-20roles-20of-20succinate-20and-20inhibition-20of-20SDH-20in-20metabolic-20reprograming-20towards-20a-20malignant-20phenotype." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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