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ID 10617
Eprint ID
10617
FullText URL
Thumnail O004090.pdf 114 KB
Title Alternative
メタンフェタミン誘発ドパミン神経毒性はキノン体形成関連分子により調節されている
Author
Abstract
Recently, the neurotoxicity of dopamine (DA) quinone formation by auto-oxidation of DA has focused on dopaminergic neuron-specific oxidative stress. In the present study, we examined DA quinone formation in methamphetamine (METH)-induced dopaminergic neuronal cell death using METH-treated dopaminergic cultured CATH.a cells and METH-injected mouse brain. In CATH.a cells, METH treatment dose-dependently increased the levels of quinoprotein (protein-bound quinone) and the expression of quinone reductase in parallel with neurotoxicity. A similar increase in quinoprotein levels was seen in the striatum of METH (4 mg/kg X4, i.p., 2 h interval)-injected BALB/c mice, coinciding with reduction of DA transporters. Furthermore, pretreatment of CATH.a cells with quinone reductase inducer, butylated hydroxyanisole, significantly and dose-dependently blocked METH-induced elevation of quinoprotein, and ameliorated METH-induced cell death. We also showed the protective effect of tyrosinase, which rapidly oxidizes DA and DA quinone to form stable melanin, against METH-induced dopaminergic neurotoxicity in vitro and in vivo using tyrosinase null mice. Our results indicate that DA quinone formation plays an important role, as a dopaminergic neuron-specific neurotoxic factor, in METH-induced neurotoxicity, which is regulated by quinone formation-related molecules.
Keywords
dopamine quinone
quinone reductase
tyrosinase
Note
http://dx.doi.org/10.1096/fj.05-4996fje
Published Date
2006-03-24
Publication Title
Content Type
Thesis or Dissertation
Grant Number
乙第4090号
Granted Date
2006-03-24
Thesis Type
博士(医学)
Grantor
岡山大学
Official Url
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16403784&dopt=Abstract
language
日本語
File Version
none
Refereed
Unknown