Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 K scrapie agent
Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 K scrapie agent
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DOI：
10.1007/s004010050895
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发表时间：
1998-09-01
影响因子：
12.7
通讯作者：
Kim, YS
中科院分区：
文献类型：
--
作者：
Choi, SI;Ju, WK;Kim, YS
羊瘙痒病是绵羊和其他动物的一种传染性神经退行性疾病，属于朊病毒病。朊病毒疾病的临床症状的特征是潜伏期长，随后是进行性共济失调、震颤和死亡。为了研究羊瘙痒病感染过程中神经退行性变的诱导，我们分析了羊瘙痒病感染仓鼠大脑皮层、脑干和小脑中各种抗氧化酶和线粒体酶的活性。线粒体Mn-超氧化物歧化酶（SOD）活性降低，而胞浆Cu/Zn-SOD和过氧化氢酶活性无明显变化。羊瘙痒病感染仓鼠的谷胱甘肽过氧化物酶和谷胱甘肽还原酶的活性增加。Mn-SOD活性的降低可能导致感染脑线粒体中氧化应激的增加;我们的研究结果支持这一概念，即感染脑线粒体中的高水平脂质过氧化，低水平ATP酶和细胞色素c氧化酶活性。此外，在感染脑的海马和大脑皮层的神经元中观察到线粒体结构异常。这些结果表明，氧化应激引起的线粒体功能障碍引起朊病毒病的神经变性。
Scrapie, one of the prion diseases, is a transmissible neurodegenerative disease of sheep and other animals. Clinical symptoms of prion diseases are characterized by a long latent period, followed by progressive ataxia, tremor, and death. To study the induction of neurodegeneration during scrapie infection, we have analyzed the activities of various antioxidant enzymes and mitochondrial enzymes in cerebral cortex, brain stem, and cerebellum of scrapie-infected hamsters. The activity of mitochondrial Mn-superoxide dismutase (SOD) was decreased, while the activities of cytosolic Cu/Zn-SOD and catalase were not altered in infected brains. The activities of glutathione peroxidase and glutathione reductase were increased in scrapie-infected hamsters. The decreased activity of Mn-SOD might result in increasing oxidative stress in the mitochondria of infected brain; this concept is supported by our findings of a high level of lipid peroxidation, and low levels of ATPase and cytochrome c oxidase activity in the infected cerebral mitochondria. In addition, structural abnormalities of mitochondria have been observed in the neurons of hippocampus and cerebral cortex of infected brain. These results suggest that mitochondrial dysfunction caused by oxidative stress gives rise to neurodegeneration in prion disease.