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 |
|---|---|
| Pages (from-to) | 5003-5008 |
| Number of pages | 6 |
| Journal | FEBS Letters |
| Volume | 581 |
| Issue number | 25 |
| DOIs | |
| Publication status | Published - Oct 16 2007 |
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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 journal › Article
}
TY - JOUR
T1 - Protective effects of metallothionein against dopamine quinone-induced dopaminergic neurotoxicity
AU - Miyazaki, Ikuko
AU - Asanuma, Masato
AU - Hozumi, Hiroaki
AU - Miyoshi, Ko
AU - Sogawa, Norio
PY - 2007/10/16
Y1 - 2007/10/16
N2 - 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.
AB - 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.
KW - Dopamine quinone
KW - Metallothionein
KW - Parkinson's disease
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=34948859040&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34948859040&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2007.09.046
DO - 10.1016/j.febslet.2007.09.046
M3 - Article
C2 - 17910954
AN - SCOPUS:34948859040
VL - 581
SP - 5003
EP - 5008
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 25
ER -