Methamphetamine-induced Dopaminergic Neurotoxicity is Regulated by Quinone-formation-related Molecules.
From: Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publish Date: Mar 2006
- ISSN: 1530-6860
- Volume: 20
- Issue: 3
- Pages: 571-3
- Medium: Internet
- Language: English
- Citation (JAMA): Miyazaki Ikuko, Asanuma Masato, Diaz-Corrales Francisco J, et al. Methamphetamine-induced Dopaminergic Neurotoxicity is Regulated by Quinone-formation-related Molecules.. FASEB J. Mar 2006;20:571-3
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.
Mesh Headings (Keywords): Animals, Brain Chemistry, Butylated Hydroxyanisole, Corpus Striatum, Dopamine, Dopamine Plasma Membrane Transport Proteins, Enzyme Induction, Male, Melanins, Methamphetamine, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Mutant Strains, Monophenol Monooxygenase, NAD(P)H Dehydrogenase (Quinone), NADPH Dehydrogenase, Nerve Tissue Proteins, Neurons, Oxidative Stress
Check for Full Text / PubMed Unique Identifier (PMID): 16403784
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