Abstract
Dopamine (DA) quinone as DA neuron-specific oxidative stress conjugates with cysteine residues in functional proteins to form quinoproteins. Here, we examined the effects of cysteine-rich metal-binding proteins, metallothionein (MT)-1 and -2, on DA quinone-induced neurotoxicity. MT quenched DA semiquinones in vitro. In dopaminergic cells, DA exposure increased quinoproteins and decreased cell viability; these were ameliorated by pretreatment with MT-inducer zinc. Repeated L-DOPA administration markedly elevated striatal quinoprotein levels and reduced the DA nerve terminals specifically on the lesioned side in MT-knockout parkinsonian mice, but not in wild-type mice. Our results suggested that intrinsic MT protects against L-DOPA-induced DA quinone neurotoxicity in parkinsonian mice by its quinone-quenching property.
Original language | English |
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Pages (from-to) | 5003-5008 |
Number of pages | 6 |
Journal | FEBS Letters |
Volume | 581 |
Issue number | 25 |
DOIs | |
Publication status | Published - Oct 16 2007 |
Keywords
- Dopamine quinone
- Metallothionein
- Parkinson's disease
- Zinc
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology