Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, and efficacious antioxidant therapy in superoxide dismutase 2 null mice

• DOI: 10.1046/j.1471-4159.2003.02195.x
• Publication Date: 2005-07-28T21:33:56Z
• Authors: Douglas Hinerfeld; Mathew D. Traini; Ron P. Weinberger; Bruce Cochran; Susan R. Doctrow; Jenny Harry; Simon Melov
• Keywords: SOD2; Mitochondrial respiratory chain

Abstract Oxidative stress and mitochondrial dysfunction have been linked to neurodegenerative disorders such as Parkinson's Alzheimer's disease. However, it is not yet understood how endogenous oxidative may result in dysfunction. Most prior studies tested paradigms mitochondria through either chemical inhibition of specific components the respiratory chain, or adding an exogenous insult hydrogen peroxide paraquat directly damage mitochondria. In contrast, mice that lack superoxide dismutase (SOD2 null mice) represent a model stress. SOD2 develop severe neurological phenotype includes behavioral defects, spongiform encephalopathy, decrease aconitase activity. We hypothesis chain brain were differentially sensitive stress, whether sensitivity would lead neuronal cell death. carried out proteomic differential display examined activities complexes I, II, III, IV, V, tricarboxylic acid cycle enzymes alpha‐ketoglutarate dehydrogenase citrate synthase conjunction with efficacious antioxidant treatment observed sensitivities proteins addition, we striking pattern death able significantly reduce loss neurons via treatment.