title: Proteomic analysis of rat brain mitochondria following exposure to dopamine quinone: implications for Parkinson disease.
abstract: Oxidative stress and mitochondrial dysfunction have been linked to dopaminergic neuron degeneration in Parkinson disease. We have previously shown that dopamine oxidation leads to selective dopaminergic terminal degeneration in vivo and alters mitochondrial function in vitro. In this study, we utilized 2-D difference in-gel electrophoresis to assess changes in the mitochondrial proteome following in vitro exposure to reactive dopamine quinone. A subset of proteins exhibit decreased fluorescence labeling following dopamine oxidation, suggesting a rapid loss of specific proteins. Amongst these proteins are mitochondrial creatine kinase, mitofilin, mortalin, the 75 kDa subunit of NADH dehydrogenase, and superoxide dismutase 2. Western blot analyses for mitochondrial creatine kinase and mitofilin confirmed significant losses in isolated brain mitochondria exposed to dopamine quinone and PC12 cells exposed to dopamine. These results suggest that specific mitochondrial proteins are uniquely susceptible to changes in abundance following dopamine oxidation, and carry implications for mitochondrial stability in Parkinson disease neurodegeneration.
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Van Laar
authors.forename: April A
authors.initials: AA
authors.lastname: Dukes
authors.forename: Michael
authors.initials: M
authors.lastname: Cascio
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Hastings
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D024101:Mitochondrial Proteins; C104705:dopamine quinone; D004298:Dopamine