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

Biochim Biophys Acta. 1997 Nov 28;1362(1):77-86. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Animals
  • 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 / metabolism
  • Neuroblastoma
  • Neurons / enzymology
  • Neurons / metabolism*
  • Oxidative Stress
  • Parkinson Disease, Secondary / enzymology
  • Parkinson Disease, Secondary / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / metabolism
  • Tumor Cells, Cultured


  • Antioxidants
  • Reactive Oxygen Species
  • Hydroxyl Radical
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase