Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of Parkinson's disease

• Published in: Biochimica et biophysica acta Vol. 1362; no. 1; pp. 77 - 86
• Main Authors: Cassarino, David S, Fall, Christopher P, Swerdlow, Russell H, Smith, Trisha S, Halvorsen, Erik M, Miller, Scott W, Parks, Janice P, Parker, W.Davis, Bennett, James P
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.11.1997
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology; Animals; Antioxidant enzymes; Antioxidants - metabolism; Brain - enzymology; Brain - metabolism; Catalase - metabolism; Disease Models, Animal; Glutathione Peroxidase - metabolism; Glutathione Reductase - metabolism; Humans; Hybrid Cells; Hydroxyl Radical - metabolism; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondria - metabolism; MPTP; Neuroblastoma; Neurons - enzymology; Neurons - metabolism; Oxidative Stress; Parkinson Disease, Secondary - enzymology; Parkinson Disease, Secondary - metabolism; Parkinson's disease; Reactive oxygen species; Reactive Oxygen Species - metabolism; Superoxide Dismutase - metabolism; Tumor Cells, Cultured; Mitochondria; Reactive oxygen species; Parkinson's disease; MPTP; Antioxidant enzymes
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/S0925-4439(97)00070-7

The dopaminergic neurotoxin N-methyl,4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) causes a syndrome in primates and humans which mimics Parkinson's disease (PD) in clinical, pathological, and biochemical findings, including diminished activity of complex I in the mitochondrial electron transport chain. Reduced complex I activity is found in sporadic PD and can be transferred through mitochondrial DNA, suggesting a mitochondrial genetic etiology. We now show that MPTP treatment of mice and N-methylpyridinium (MPP +) exposure of human SH-SY5Y neuroblastoma cells increases oxygen free radical production and antioxidant enzyme activities. Cybrid cells created by transfer of PD mitochondria exhibit similar characteristics; however, PD cybrids' antioxidant enzyme activities are not further increased by MPP + exposure, as are the activities in control cybrids. PD mitochondrial cybrids are subject to metabolic and oxidative stresses similar to MPTP parkinsonism and provide a model to determine mechanisms of oxidative damage and cell death in PD.