Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of Parkinson's disease
Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of Parkinson's disease
复制标题
DOI：
10.1016/s0925-4439(97)00070-7
复制
发表时间：
1997-11-28
影响因子：
6.2
通讯作者：
Bennett, JP
中科院分区：
文献类型：
--
作者：
Cassarino, DS;Fall, CP;Bennett, JP
多巴胺能神经毒素N-甲基，4-苯基-1，2，3，6-四氢吡啶（MPTP）在灵长类动物和人类中引起一种综合征，在临床、病理和生化方面与帕金森病（PD）相似，包括线粒体电子传递链中复合物I活性降低。在散发性PD中发现复合物I活性降低，并且可以通过线粒体DNA转移，表明线粒体遗传病因学。我们现在表明，MPTP治疗小鼠和N-甲基吡啶（MPP+）暴露的人SH-SY 5 Y神经母细胞瘤细胞增加氧自由基的产生和抗氧化酶的活性。通过转移PD线粒体产生的胞质杂种细胞表现出相似的特征;然而，PD胞质杂种的抗氧化酶活性不像对照胞质杂种中的活性那样通过MPP+暴露进一步增加。PD线粒体胞质杂交体受到类似于MPTP帕金森综合征的代谢和氧化应激，并提供了一个模型来确定PD中氧化损伤和细胞死亡的机制。(C)1997年Elsevier Science B.V.
The dopaminergic neurotoxin N-methyl,4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) causes a syndrome in primates and humans which mimics Parkinson's disease (PD) in clinical, pathological, and biochemical findings, including diminished activity of complex I in the mitochondrial electron transport chain. Reduced complex I activity is found in sporadic PD and can be transferred through mitochondrial DNA, suggesting a mitochondrial genetic etiology. We now show that MPTP treatment of mice and N-methylpyridinium (MPP+) exposure of human SH-SY5Y neuroblastoma cells increases oxygen free radical production and antioxidant enzyme activities. Cybrid cells created by transfer of PD mitochondria exhibit similar characteristics; however, PD cybrids' antioxidant enzyme activities are not further increased by MPP+ exposure, as are the activities in control cybrids. PD mitochondrial cybrids are subject to metabolic and oxidative stresses similar to MPTP parkinsonism and provide a model to determine mechanisms of oxidative damage and cell death in PD. (C) 1997 Elsevier Science B.V.