Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease

Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease
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DOI:
10.1016/s0197-4580(01)00314-1
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发表时间:
2002-05-01
影响因子:
4.2
通讯作者:
Solaini, G
Solaini, G
中科院分区:
医学2区
文献类型:
--
作者:
Bosetti, F;Brizzi, F;Solaini, G

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有证据表明,线粒体功能障碍在阿尔茨海默病(AD)中很突出。一个或多个线粒体电子传递链酶或f1f0 -ATP合成酶(ATP合成酶)的失效可能损害大脑能量储存,产生有害的活性氧(ROS)。并导致神经元死亡本研究采用细胞色素c氧化酶(COX)和f1f0 - atp酶(f1f0 - atp酶)活性测定方法,测定了AD患者和同龄对照者的血小板、死后运动皮质和海马分离线粒体的活性。与对照组相比,血小板(-30%,P < 0.01, n = 20)和海马(- 35% ~ -40%)COX活性显著降低。P < 0.05, n = 6),但在AD患者的运动皮层中没有。相比之下,在AD血小板和脑组织中,F1F0-ATP水解活性没有显著变化。此外,AD患者和对照组血小板线粒体中ATP合成率相似。这些结果表明,COX是AD的线粒体靶点,而不是f1f0 - atp酶。在脑联合区和血小板中。COX活性降低可能使组织易受兴奋性毒性或氧可用性降低的影响。缩写:β:淀粉样蛋白;AD:阿尔茨海默病;COX:细胞色素氧化酶os - atp酶;寡霉素敏感atp酶;ROS:活性氧。(C) 2002爱思唯尔科学有限公司版权所有。
Evidence suggests that mitochondrial dysfunction is prominent in Alzheimer's disease (AD). A failure of one or more of the mitochondrial electron transport chain enzymes or of F1F0-ATPase (ATP synthase) could compromise brain energy stores, generate damaging reactive oxygen species (ROS). and lead to neuronal death. fit the present study, cytochrome c oxidase (COX) and F1F0-ATPase activities of isolated mitochondria from platelets and postmortem motor cortex and hippocampus from AD patients and age-matched control subjects were assayed. Compared with controls, COX activity was decreased significantly in platelets (-30%, P < 0.01, n = 20) and hippocampus (-35 to -40%. P < 0.05, n = 6), but not in motor cortex from the AD patients. In contrast, in AD platelets and brain tissues, F1F0-ATP hydrolysis activity was not significantly changed. Moreover, the ATP synthesis rate was similar in mitochondria of platelets from AD patients and controls. These results demonstrate that COX but not F1F0-ATPase is a mitochondrial target in AD. in both a brain association area and in platelets. A reduced COX activity may make the tissue vulnerable to excitotoxicity or reduced oxygen availability. Abbreviations: Abeta: amyloid betas AD: Alzheimer's disease; COX: cytochrome oxidase OS-ATPase: oligomycin-sensitive ATPase: ROS: reactive oxygen species. (C) 2002 Elsevier Science Inc. All rights reserved.