Increased glutathione levels in cortical and striatal mitochondria of the R6/2 Huntington's disease mouse model
Increased glutathione levels in cortical and striatal mitochondria of the R6/2 Huntington's disease mouse model
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DOI：
10.1016/j.neulet.2005.05.065
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发表时间：
2005-09-01
影响因子：
2.5
通讯作者：
Lesort, M
中科院分区：
文献类型：
--
作者：
Choo, YS;Mao, ZK;Lesort, M
亨廷顿氏病（HD）是一种进行性神经退行性疾病，其特征是主要发生在新纹状体的严重神经元损失。据推测，线粒体功能障碍和氧化应激可能在疾病的病因学中起重要作用。事实上，氧化应激损伤的标志物已经在HD患者的大脑和HD的小鼠模型中检测到。在这项研究中，我们评估了一种广泛研究的HD小鼠模型（R6/2）的皮质和纹状体中强效内源性抗氧化剂谷胱甘肽和参与其代谢或再循环的酶的水平变化。在皮质和纹状体中，与同窝野生型对照组相比，R6/2小鼠的细胞谷胱甘肽水平无显著差异。值得注意的是，与野生型对照小鼠相比，从R6/2小鼠的皮质和纹状体分离的线粒体中谷胱甘肽的水平显著增加。线粒体中谷胱甘肽水平的这种特异性增加表明，在R6/2小鼠中诱导了一种补偿机制，以防止线粒体中氧化应激的增加。(C)2005爱思唯尔爱尔兰有限公司保留所有权利。
Huntington's disease (HD) is a progressive neurodegenerative disease characterized by a severe neuronal loss that occurs primarily in the neostriatum. It has been postulated that mitochondria dysfunction and oxidative stress may play significant roles in the etiology of the disease. Indeed, markers of oxidative stress damage have been detected in the brains of HD patients and in mouse models of HD. In this study, we evaluate the changes in the levels of the potent, endogenous antioxidant glutathione and enzymes involved in its metabolism or recycling in the cortex and striatum of an extensively studied HD mouse model (R6/2). In both cortex and striatum, the levels of cellular glutathione were not significantly different in the R6/2 mice when compared with littermate wild type controls. Remarkably, the levels of glutathione were significantly increased in mitochondria isolated from the cortex and striatum of R6/2 mice when compared with wild type control mice. This specific increase in the levels of glutathione in mitochondria suggests that a compensatory mechanism is induced in the R6/2 mice to protect against an increase in oxidative stress in mitochondria. (C) 2005 Elsevier Ireland Ltd. All rights reserved.