EXCESS BRAIN PROTEIN OXIDATION AND ENZYME DYSFUNCTION IN NORMAL AGING AND IN ALZHEIMER-DISEASE
EXCESS BRAIN PROTEIN OXIDATION AND ENZYME DYSFUNCTION IN NORMAL AGING AND IN ALZHEIMER-DISEASE
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DOI：
10.1073/pnas.88.23.10540
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发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
MARKESBERY, WR
中科院分区：
文献类型：
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作者：
SMITH, CD;CARNEY, JM;MARKESBERY, WR
阿尔茨海默病（AD）与衰老之间的关系目前尚不清楚。在这项研究中，从16名阿尔茨海默病患者、8名年龄匹配的对照者和5名年轻对照者获取了死后的额极和枕极脑样本。对这些样本既分析了蛋白质氧化产物（羰基），也分析了两种易受混合功能氧化影响的酶——谷氨酰胺合成酶和肌酸激酶的活性。谷氨酰胺合成酶比肌酸激酶对混合功能氧化更敏感。羰基含量随年龄呈指数增长，额极的增长速度是枕极的两倍。与年轻对照者相比，两个老年组（阿尔茨海默病组和年龄匹配的对照组）的羰基含量都增加了，谷氨酰胺合成酶和肌酸激酶的活性都降低了，而且在所有情况下，额极的变化都比枕极更显著。我们得出结论：蛋白质氧化产物在大脑中积累，易受氧化的酶活性随着衰老以相同的区域模式（额极比枕极受影响更严重）而降低。然而，只有谷氨酰胺合成酶活性能够将阿尔茨海默病与年龄匹配的对照组区分开来：因为在阿尔茨海默病中额极的谷氨酰胺合成酶活性有差异地降低，我们认为阿尔茨海默病可能代表大脑对年龄相关氧化的一种特定易感性。
The relationship between Alzheimer disease (AD) and aging is not currently known. In this study, postmortem frontal- and occipital-pole brain samples were obtained from 16 subjects with AD, 8 age-matched controls, and 5 young controls. These samples were analyzed both for protein oxidation products (carbonyl) and the activities of two enzymes vulnerable to mixed-function oxidation, glutamine synthetase and creatine kinase. Glutamine synthetase is more sensitive to mixed-function oxidation than creatine kinase. Carbonyl content rises exponentially with age, at double the rate in the frontal pole compared with the occipital pole. Compared with young controls, both aged groups (AD and age-matched controls) have increased carbonyl content and decreased glutamine synthetase and creatine kinase activities, which are more marked in the frontal than occipital pole in all instances. We conclude that protein oxidation products accumulate in the brain and that oxidation-vulnerable enzyme activities decrease with aging in the same regional pattern (frontal more affected than occipital). However, only glutamine synthetase activity distinguishes AD from age-matched controls: Because glutamine synthetase activity is differentially reduced in the frontal pole in AD, we suggest that AD may represent a specific brain vulnerability to age-related oxidation.