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Property "Has-20abstract" (as page type) with input value "-27-27'OBJECTIVE:-27-27'-20Impairments-20in-20mitochondrial-20function-20have-20been-20proposed-20to-20play-20a-20role-20in-20the-20etiology-20of-20diabetic-20sensory-20neuropathy.-20We-20tested-20the-20hypothesis-20that-20mitochondrial-20dysfunction-20in-20axons-20of-20sensory-20neurons-20in-20type-201-20diabetes-20is-20due-20to-20abnormal-20activity-20of-20the-20respiratory-20chain-20and-20an-20altered-20mitochondrial-20proteome.-0A-0A-27-27'RESEARCH-20DESIGN-20AND-20METHODS:-27-27'-20Proteomic-20analysis-20using-20stable-20isotope-20labeling-20with-20amino-20acids-20in-20cell-20culture-20(SILAC)-20determined-20expression-20of-20proteins-20in-20mitochondria-20from-20dorsal-20root-20ganglia-20(DRG)-20of-20control,-2022-2Dweek-2Dold-20streptozotocin-20(STZ)-2Ddiabetic-20rats,-20and-20diabetic-20rats-20treated-20with-20insulin.-20Rates-20of-20oxygen-20consumption-20and-20complex-20activities-20in-20mitochondria-20from-20DRG-20were-20measured.-20Fluorescence-20imaging-20of-20axons-20of-20cultured-20sensory-20neurons-20determined-20the-20effect-20of-20diabetes-20on-20mitochondrial-20polarization-20status,-20oxidative-20stress,-20and-20mitochondrial-20matrix-2Dspecific-20reactive-20oxygen-20species-20(ROS).-0A-0A-27-27'RESULTS:-27-27'-20Proteins-20associated-20with-20mitochondrial-20dysfunction,-20oxidative-20phosphorylation,-20ubiquinone-20biosynthesis,-20and-20the-20citric-20acid-20cycle-20were-20downregulated-20in-20diabetic-20samples.-20For-20example,-20cytochrome-20c-20oxidase-20subunit-20IV-20(COX-20IV-3B-20a-20Complex-20IV-20protein)-20and-20NADH-20dehydrogenase-20Fe-2DS-20protein-203-20(NDUFS3-3B-20a-20Complex-20I-20protein)-20were-20reduced-20by-2029-20and-2036-25-20(-27-27P-27-27-20-3C-200.05),-20respectively,-20in-20diabetes-20and-20confirmed-20previous-20Western-20blot-20studies.-20Respiration-20and-20mitochondrial-20complex-20activity-20was-20significantly-20decreased-20by-2015-20to-2032-25-20compared-20with-20control.-20The-20axons-20of-20diabetic-20neurons-20exhibited-20oxidative-20stress-20and-20depolarized-20mitochondria,-20an-20aberrant-20adaption-20to-20oligomycin-2Dinduced-20mitochondrial-20membrane-20hyperpolarization,-20but-20reduced-20levels-20of-20intramitochondrial-20superoxide-20compared-20with-20control.-0A-0A-27-27'CONCLUSIONS:-27-27'-20Abnormal-20mitochondrial-20function-20correlated-20with-20a-20downregulation-20of-20mitochondrial-20proteins,-20with-20components-20of-20the-20respiratory-20chain-20targeted-20in-20lumbar-20DRG-20in-20diabetes.-20The-20reduced-20activity-20of-20the-20-5B-5Brespiratory-20chain-5D-5D-20was-20associated-20with-20diminished-20superoxide-20generation-20within-20the-20mitochondrial-20matrix-20and-20did-20not-20contribute-20to-20oxidative-20stress-20in-20axons-20of-20diabetic-20neurons.-20Alternative-20pathways-20involving-20polyol-20pathway-20activity-20appear-20to-20contribute-20to-20raised-20ROS-20in-20axons-20of-20diabetic-20neurons-20under-20high-20glucose-20concentration." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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