Methamphetamine-induced dopaminergic neurotoxicity is regulated by quinone-formation-related molecules.
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.
Miyazaki
Ikuko
I
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Asanuma
Masato
M
Diaz-Corrales
Francisco J
FJ
Fukuda
Masaya
M
Kitaichi
Kiyoyuki
K
Miyoshi
Ko
K
Ogawa
Norio
N
D000818:Animals; D001923:Brain Chemistry; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D008543:Melanins / Q000096:biosynthesis; D008694:Methamphetamine / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D014442:Monophenol Monooxygenase / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors; D009252:NADPH Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress
D050483:Dopamine Plasma Membrane Transport Proteins; D008543:Melanins; D009419:Nerve Tissue Proteins; D002083:Butylated Hydroxyanisole; D008694:Methamphetamine; C104705:dopamine quinone; D014442:Monophenol Monooxygenase; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D009252:NADPH Dehydrogenase; D004298:Dopamine