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Methamphetamine‐induced dopaminergic neurotoxicity is regulated by quinone formation‐related molecules
Author(s) -
Miyazaki Ikuko,
Asanuma Masato,
DiazCorrales Francisco J.,
Fukuda Masaya,
Kitaichi Kiyoyuki,
Miyoshi Ko,
Ogawa Norio
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4996fje
Subject(s) - neurotoxicity , meth , dopaminergic , chemistry , pharmacology , oxidative stress , methamphetamine , tyrosinase , pyrroloquinoline quinone , biochemistry , dopamine , biology , enzyme , toxicity , neuroscience , cofactor , monomer , organic chemistry , acrylate , polymer
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.