Pramipexole Reduces Reactive Oxygen Species Production In Vivo and In Vitro and Inhibits the Mitochondrial Permeability Transition Produced by the Parkinsonian Neurotoxin Methylpyridinium Ion
Version of Record online: 13 NOV 2002
Journal of Neurochemistry
Volume 71, Issue 1, pages 295–301, July 1998
How to Cite
Cassarino, D. S., Fall, C. P., Smith, T. S. and Bennett, J. P. (1998), Pramipexole Reduces Reactive Oxygen Species Production In Vivo and In Vitro and Inhibits the Mitochondrial Permeability Transition Produced by the Parkinsonian Neurotoxin Methylpyridinium Ion. Journal of Neurochemistry, 71: 295–301. doi: 10.1046/j.1471-4159.1998.71010295.x
- Issue online: 13 NOV 2002
- Version of Record online: 13 NOV 2002
- Received November 19, 1997; revised manuscript received January 27, 1998; accepted January 28, 1998.
- Parkinson's disease;
- Oxygen free radicals;
- Mitochondrial permeability transition pore
Abstract: Sporadic Parkinson's disease is associated with a defect in the activity of complex I of the mitochondrial electron transport chain. This electron transport chain defect is transmitted through mitochondrial DNA, and when expressed in host cells leads to increased oxygen free radical production, increased antioxidant enzyme activities, and increased susceptibility to programmed cell death. Pramipexole, a chemically novel dopamine agonist used for the treatment of Parkinson's disease symptoms, possesses antioxidant activity and is neuroprotective toward substantia nigral dopamine neurons in hypoxic-ischemic and methamphetamine models. We found that pramipexole reduced the levels of oxygen radicals produced by methylpyridinium ion (MPP+) both when incubated with SH-SY5Y cells and when perfused into rat striatum. Pramipexole also exhibited a concentration-dependent inhibition of opening of the mitochondrial transition pore induced by calcium and phosphate or MPP+. These results suggest that pramipexole may be neuroprotective in Parkinson's disease by attenuating intracellular processes such as oxygen radical generation and the mitochondrial transition pore opening, which are associated with programmed cell death.