A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients
A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients
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DOI：
10.1016/s0197-4580(00)00112-3
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发表时间：
2000-05-01
影响因子：
4.2
通讯作者：
Möller, HJ
中科院分区：
文献类型：
--
作者：
Maurer, I;Zierz, S;Möller, HJ
为了评估线粒体功能并检验阿尔茨海默病（AD）中潜在氧化磷酸化缺陷的假设，我们评估了额叶皮质、颞叶皮质和海马中线粒体呼吸链酶复合体I+III、复合体II+III、复合体IV（细胞色素c氧化酶，考克斯）、琥珀酸dt氢化酶和柠檬酸合酶的活性。23例AD患者和13例正常人的大脑皮层和小脑。主要发现是AD颞叶皮层和海马的考克斯活性显著降低，无论活性是否表达于非胶原蛋白含量（49 +/- 4.6 vs. 78 +/- 10.8 nmol/min/mg NCP，P = 0.006; 23 +/- 1.9 vs. 48.6 +/- 8.1 nmol/min/tng NCP，p = 0.003）或校正柠檬酸合酶活性（1.6 +/- 0.2对比3 +/- 0.4，P = 0.001;0.76 +/- 0.1对比1.76 +/- 0.26，P = 0.0009）。复合物I+III，II+III和琥珀酸脱氢酶在任何大脑区域检查的活动没有显着差异。我们的结果表明，与正常人脑相比，AD脑中的考克斯存在特定缺陷，这可能导致能量产生受损。从生物化学上讲，这种缺陷仅限于选定的大脑区域，这表明了解剖学上的特异性。(C)2000 Elsevier Science Inc. All rights reserved.
To assess mitochondrial function and test the hypothesis of an underlying oxidative phosphorylation defect in Alzheimer disease (AD), we evaluated the activities of mitochondrial respiratory chain enzyme complexes I+III, complexes II+III, complex IV (cytochrome c oxidase, COX), succinate dt hydrogenase, and citrate synthase in the frontal cortex, temporal cortex, hippocampus. and cerebellum of 23 AD patients and 13 normal human brains. The major finding was a significant decrease in COX activity in AD temporal cortex and hippocampus, both whether activities were expressed per noncollagen protein content (49 +/- 4.6 versus 78 +/- 10.8 nmol/min/mg NCP, P = 0.006; 23 +/- 1.9 versus 48.6 +/- 8.1 nmol/min/tng NCP, p = 0.003) or corrected for citrate synthase activity (1.6 +/- 0.2 versus 3 +/- 0.4, P = 0.001;0.76 +/- 0.1 versus 1.76 +/- 0.26, P = 0.0009). There were no significant differences in the activities of complexes I+III, II+III, and of succinate dehydrogenase in any of the brain regions examined. Out results suggest a specific defect of COX in the AD brain versus the normal human brain, which may contribute to impaired energy generation. Biochemically, the defect is confined to selected brain regions, suggesting anatomic specificity. (C) 2000 Elsevier Science Inc. All rights reserved.