Superoxide dismutase/catalase mimetics are neuroprotective against selective paraquat-mediated dopaminergic neuron death in the substantial nigra - Implications for Parkinson disease
Superoxide dismutase/catalase mimetics are neuroprotective against selective paraquat-mediated dopaminergic neuron death in the substantial nigra - Implications for Parkinson disease
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DOI：
10.1074/jbc.m500984200
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发表时间：
2005-08-12
影响因子：
4.8
通讯作者：
Andersen, JK
中科院分区：
文献类型：
--
作者：
Peng, J;Stevenson, FF;Andersen, JK
已证实，小鼠暴露于除草剂百草枯可导致黑质致密部(SNPC)多巴胺能神经元选择性丧失，类似于帕金森病(PD)。在这项研究中，我们研究了两种人工合成的超氧化物歧化酶/过氧化氢酶模拟物(EUK-134和EUK-189)在体外和成年小鼠体内对百草枯诱导的多巴胺能细胞系1RB(3)和(27)(N27)和原代培养的中脑细胞死亡的保护作用。我们的数据表明，EUK-134或EUK-189在体外以浓度依赖的方式显著减轻百草枯诱导的神经毒性。此外，全身应用EUK-189可减少体内百草枯介导的SNPC多巴胺能神经元细胞死亡。这些发现支持氧化应激在百草枯诱导的神经毒性中的作用，并为与氧化应激相关的神经退行性疾病(如帕金森病)提出了新的治疗方法。
Exposure of mice to the herbicide paraquat has been demonstrated to result in the selective loss of dopaminergic neurons of the substantia nigra, pars compacta (SNpc) akin to what is observed in Parkinson disease (PD). In this study, we investigate the efficacy of two synthetic superoxide dismutase/catalase mimetics (EUK-134 and EUK-189) in protecting against paraquat-induced dopaminergic cell death in both the rat dopaminergic cell line 1RB(3)AN(27) (N27) and primary mesencephalic cultures in vitro and in adult mice in vivo. Our data demonstrate that pretreatment with either EUK-134 or EUK-189 significantly attenuates paraquat-induced neurotoxicity in vitro in a concentration-dependent manner. Furthermore, systemic administration of EUK-189 decreases paraquat-mediated SNpc dopaminergic neuronal cell death in vivo. These findings support a role for oxidative stress in paraquat-induced neurotoxicity and suggest novel therapeutic approaches for neurodegenerative disorders associated with oxidative stress such as PD.