Protective effects of metallothionein against dopamine quinone-induced dopaminergic neurotoxicity

Ikuko Miyazaki, Masato Asanuma, Hiroaki Hozumi, Ko Miyoshi, Norio Sogawa

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 languageEnglish
Pages (from-to)5003-5008
Number of pages6
JournalFEBS Letters
Volume581
Issue number25
DOIs
Publication statusPublished - Oct 16 2007

Keywords

  • Dopamine quinone
  • Metallothionein
  • Parkinson's disease
  • Zinc

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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