ELEVATED REACTIVE OXYGEN SPECIES AND ANTIOXIDANT ENZYME-ACTIVITIES INANIMAL AND CELLULAR-MODELS OF PARKINSONS-DISEASE

The dopaminergic neurotoxin N-methyl,4-phenyl-1,2,3,6 tetrahydropyridi ne (MPTP) causes a syndrome in primates and humans which mimics Parkin son's disease (PD) in clinical, pathological, and biochemical findings , including diminished activity of complex I in the mitochondrial elec tron transport chain. Reduced complex I activity is found in sporadic PD and can be transferred through mitochondrial DNA, suggesting a mito chondrial genetic etiology. We now show that MPTP treatment of mice an d N-methylpyridinium (MPP+) exposure of human SH-SY5Y neuroblastoma ce lls increases oxygen free radical production and antioxidant enzyme ac tivities. Cybrid cells created by transfer of PD mitochondria exhibit similar characteristics; however, PD cybrids' antioxidant enzyme activ ities are not further increased by MPP+ exposure, as are the activitie s in control cybrids. PD mitochondrial cybrids are subject to metaboli c and oxidative stresses similar to MPTP parkinsonism and provide a mo del to determine mechanisms of oxidative damage and cell death in PD. (C) 1997 Elsevier Science B.V.