Journal
BRAIN RESEARCH
Volume 881, Issue 2, Pages 182-189Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0006-8993(00)02841-9
Keywords
catalase; dopaminergic neurons; oxidative stress; Parkinson's disease; reactive oxygen species; superoxide dismutase
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Oxidative stress has been implicated in the selective degeneration of dopaminergic (DAergic) neurons in Parkinson's disease (PD). In this study, we tested the efficacy of EUK-134, a superoxide dismutase (SOD) and catalase mimetic, on the nitration of tyrosine hydroxylase (TH), a marker of oxidative stress, and neurotoxicity produced by 1-methyl-4-phenylpyridinium (MPP+) and 6-hydroxydopamine (6-OHDA) in primary DAergic neuron cultures. Exposure of cultures to 10 muM MPP+ reduced dopamine (DA) uptake and the number of tyrosine hydroxylase immunoreactive (THir) neurons to 56 and 52% of control, while exposure to 30 muM 6-OHDA reduced DA uptake and the number of THir neurons to 58 and 59% of control, respectively. Pretreatment of cultures with 0.5 muM EUK-134 completely protected DAergic neurons against MPP+- and 6-OHDA-induced neurotoxicity. Exposure of primary neuron cultures to either MPP+ or 6-OHDA produced nitration of tyrosine residues in TH. Pretreatment of cultures with 0.5 muM EUK-134 completely prevented MPP+- or 6-OHDA-induced nitration of tyrosine residues in TH. Taken together, these results support the idea that reactive oxygen species (ROS) are critically involved in MPP+- and 6-OHDA-induced neurotoxicity and suggest a potential therapeutic role for synthetic catalytic scavengers of ROS, such as EUK-134, in the treatment of PD. (C) 2000 Elsevier Science B.V. All rights reserved.
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