Protective effects of metallothionein against dopamine quinone-induced dopaminergic neurotoxicity.
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.
Miyazaki
Ikuko
I
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Okayama 700-8558, Japan.
Asanuma
Masato
M
Hozumi
Hiroaki
H
Miyoshi
Ko
K
Sogawa
Norio
N
D000818:Animals; D002460:Cell Line; D019610:Cytoprotection; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D015259:Dopamine Agents / Q000737:chemistry / Q000633:toxicity*; D007980:Levodopa / Q000494:pharmacology; D008668:Metallothionein / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
D015259:Dopamine Agents; C491054:Mt2 protein, mouse; D012333:RNA, Messenger; C525355:metallothionein-1, mouse; D007980:Levodopa; C104705:dopamine quinone; D016627:Oxidopamine; D008668:Metallothionein; D015032:Zinc; D004298:Dopamine