Hensley K, Hall N, Subramaniam R, Cole P, Harris M, Aksenov M, Aksenova M, Gabbita S P, Wu J F, Carney J M
Department of Chemistry, University of Kentucky, Lexington 40506-0055, USA.
J Neurochem. 1995 Nov;65(5):2146-56. doi: 10.1046/j.1471-4159.1995.65052146.x.
Four biomarkers of neuronal protein oxidation [W/S ratio of MAL-6 spin-labeled synaptosomes, phenylhydrazine-reactive protein carbonyl content, glutamine synthetase (GS) activity, creatine kinase (CK) activity] in three brain regions [cerebellum, inferior parietal lobule (IPL), and hippocampus (HIP)] of Alzheimer's disease (AD)-demented and age-matched control subjects were assessed. These endpoints indicate that AD brain protein may be more oxidized than that of control subjects. The W/S ratios of AD hippocampal and inferior parietal synaptosomes are 30 and 46% lower, respectively, than corresponding values of tissue isolated from control brain; however, the difference between the W/S ratios of AD and control cerebellar synaptosomes is not significant. Protein carbonyl content is increased 42 and 37% in the Alzheimer's HIP and IPL regions, respectively, relative to AD cerebellum, whereas carbonyl content in control HIP and IPL is similar to that of control cerebellum. GS activity decreases an average of 27% in the AD brain; CK activity declines by 80%. The brain regional variation of these oxidation-sensitive biomarkers corresponds to established histopathological features of AD (senile plaque and neurofibrillary tangle densities) and is paralleled by an increase in immunoreactive microglia. These data indicate that senile plaque-dense regions of the AD brain may represent environments of elevated oxidative stress.
对阿尔茨海默病（AD）痴呆患者及年龄匹配的对照受试者三个脑区[小脑、顶下小叶（IPL）和海马体（HIP）]中的四种神经元蛋白质氧化生物标志物[MAL-6自旋标记突触体的W/S比值、苯肼反应性蛋白质羰基含量、谷氨酰胺合成酶（GS）活性、肌酸激酶（CK）活性]进行了评估。这些终点指标表明，AD脑蛋白的氧化程度可能高于对照受试者。AD海马体和顶下小叶突触体的W/S比值分别比从对照脑分离的组织的相应值低30%和46%；然而，AD和对照小脑突触体的W/S比值之间的差异不显著。相对于AD小脑，阿尔茨海默病海马体和顶下小叶区域的蛋白质羰基含量分别增加了42%和37%，而对照海马体和顶下小叶中的羰基含量与对照小脑相似。AD脑中GS活性平均降低27%；CK活性下降80%。这些氧化敏感生物标志物的脑区差异与AD已确定的组织病理学特征（老年斑和神经原纤维缠结密度）相对应，并且与免疫反应性小胶质细胞的增加平行。这些数据表明，AD脑老年斑密集区域可能代表氧化应激升高的环境。
