Abstract
We have examined potent peroxynitrite ion (ONOO-) generator 3-morpholinosydnonimine (SIN-1)–induced neurotoxicity in control wild-type (controlwt) mice, metallothionein double knockout (MTdko) mice, metallothionein-transgenic (MTtrans) mice, and in cultured human dopaminergic (SK-N-SH) neurons to determine the neuroprotective potential of metallothionein against ONOO - induced neurodegeneratlon in Parkinson disease (PD). SIN-1–induced lipid peroxidation, reactive oxygen species synthesis, caspase-3 activation, and apoptosis were attenuated by metallothionein gene overexpression and augmented by metallothionein gene down-regulation. A progressive nigrostriatal dopaminergic neurodegeneration in weaver mutant (wv/wv) mice was associated with enhanced nitrite ion synthesis, metallothionein down-regulation, and significantly reduced dopamine synthesis and 18F-DOPA uptake as determined by high-resolution micropositron emission tomography neuroimaging. The striatal 18F-DOPA uptake was significantly higher in MTtrans mice than in MTdko and α-synuclein knockout (α-Synko) mice. These observations provide further evidence that nitric oxide synthase activation and ONOO- synthesis may be involved in the etiopathogenesls of PD, and that metallothionein gene induction may provide neuroprotection.
Keywords
Get full access to this article
View all access options for this article.
