Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis
Mitochondrial electron transport chain complex dysfunction in a transgenic mouse model for amyotrophic lateral sclerosis
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DOI：
10.1046/j.1471-4159.2002.01112.x
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发表时间：
2002-11-01
影响因子：
4.7
通讯作者：
Xu, ZS
中科院分区：
文献类型：
--
作者：
Jung, CW;Higgins, CMJ;Xu, ZS
肌萎缩侧索硬化症是一种导致运动神经元变性的致命性神经退行性疾病。铜锌超氧化物歧化酶(SOD1)基因突变是导致本病的原因之一。在小鼠中，突变蛋白的表达会导致运动神经元退化和瘫痪，类似于人类的疾病。表明线粒体受损的形态变化发生在疾病的早期阶段。为探讨线粒体功能在疾病进展过程中的变化，采用分光光度法、原位组织化学酶分析法、凝胶内组织化学结合蓝色凝胶电泳法对不同病期小鼠脊髓线粒体电子传递链酶活性进行了测定。从疾病早期开始，脊髓中的酶活性就降低了，特别是在腹角。这种下降在整个疾病发展过程中持续存在。在非转基因动物的脊髓、表达野生型蛋白的小鼠以及表达突变蛋白的小鼠的小脑和脊髓背角中没有检测到这种下降。这些结果证明了腹角区线粒体的功能缺陷，并支持线粒体损伤在突变型SOD1诱导的运动神经元变性途径中起作用的观点。
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease that causes degeneration of motoneurons. Mutation of Cu,Zn superoxide dismutase (SOD1) is one cause for this disease. In mice, expression of mutant protein causes motoneuron degeneration and paralysis resembling the human disease. Morphological change, indicative of mitochondrial damage, occurs at early stages of the disease. To determine whether mitochondrial function changes during the course of disease progression, enzyme activities of mitochondrial electron transport chain in spinal cords from mice at different disease stages were measured using three different methods: spectrophotometric assay, in situ histochemical enzyme assay, and blue native gel electrophoresis combined with in-gel histochemical reaction. The enzyme activities were decreased in the spinal cord, particularly in the ventral horn, beginning at early disease stages. This decrease persisted throughout the course of disease progression. This decrease was not detected in the spinal cords of non-transgenic animals, of mice expressing the wild-type protein, and in cerebellum and dorsal horn of the spinal cords from mice expressing mutant protein. These results demonstrate a functional defect in mitochondria in the ventral horn region and support the view that mitochondrial damage plays a role in mutant SOD1-induced motoneuron degeneration pathway.