Methamphetamine-induced dopaminergic neurotoxicity is regulated by quinone formation-related molecules
Methamphetamine-induced dopaminergic neurotoxicity is regulated by quinone formation-related molecules
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DOI：
10.1096/fj.05-4996fje
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发表时间：
2006-01-01
期刊：
影响因子：
4.8
通讯作者：
Ogawa, N
中科院分区：
文献类型：
--
作者：
Miyazaki, I;Asanuma, M;Ogawa, N
最近，通过DA自动氧化形成多巴胺（DA）醌的神经毒性集中在多巴胺能神经元特异性氧化应激上。在本研究中，我们研究了DA醌形成甲基苯丙胺（METH）诱导的多巴胺能神经元细胞死亡使用甲基苯丙胺处理的多巴胺能培养CATH。a细胞和注射MET的小鼠脑。在CATH。a细胞，METH处理剂量依赖性地增加醌蛋白（蛋白结合醌）的水平和醌还原酶的表达，与神经毒性平行。在METH（4mg/kg X4，i.p.，2 h间隔）注射的BALB/c小鼠，与DA转运蛋白的减少一致。此外，导管预处理。a细胞与醌还原酶诱导剂，丁基羟基茴香醚，显着和剂量依赖性地阻止甲基诱导的醌蛋白的升高，并改善甲基诱导的细胞死亡。我们还显示了酪氨酸酶的保护作用，它迅速氧化DA和DA醌形成稳定的黑色素，对MET诱导的多巴胺能神经毒性在体外和体内使用酪氨酸酶裸小鼠。我们的研究结果表明，DA醌的形成起着重要的作用，作为多巴胺能神经元特异性的神经毒性因子，在甲基苯丙胺诱导的神经毒性，这是由醌形成相关分子的调节。
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.