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

Fingerprint

Metallothionein
Dopamine
Cysteine
Corpus Striatum
Dopaminergic Neurons
Knockout Mice
Oxidative stress
Cell Survival
Carrier Proteins
Oxidative Stress
Metals
Neurons
Zinc
Quenching
Cells
dopamine quinone
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Protective effects of metallothionein against dopamine quinone-induced dopaminergic neurotoxicity. / Miyazaki, Ikuko; Asanuma, Masato; Hozumi, Hiroaki; Miyoshi, Ko; Sogawa, Norio.

In: FEBS Letters, Vol. 581, No. 25, 16.10.2007, p. 5003-5008.

Research output: Contribution to journalArticle

Miyazaki, Ikuko ; Asanuma, Masato ; Hozumi, Hiroaki ; Miyoshi, Ko ; Sogawa, Norio. / Protective effects of metallothionein against dopamine quinone-induced dopaminergic neurotoxicity. In: FEBS Letters. 2007 ; Vol. 581, No. 25. pp. 5003-5008.
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