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ID 10617
Eprint ID
10617
フルテキストURL
Thumnail O004090.pdf 114 KB
タイトル(別表記)
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
著者
宮﨑 育子 岡山大学
抄録
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.
キーワード
dopamine quinone
quinone reductase
tyrosinase
備考
http://dx.doi.org/10.1096/fj.05-4996fje
発行日
2006-03-24
出版物タイトル
資料タイプ
学位論文
学位授与番号
乙第4090号
学位授与年月日
2006-03-24
学位・専攻分野
博士(医学)
授与大学
岡山大学
オフィシャル URL
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16403784&dopt=Abstract
言語
Japanese
論文のバージョン
none
査読
不明