Platelet mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson Disease Research Group.
Platelet mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson Disease Research Group.
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发表时间：
1992
影响因子：
11.2
通讯作者：
D. Krige;M. Carroll;J. Cooper;C. Marsden;A. Schapira
中科院分区：
文献类型：
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作者：
D. Krige;M. Carroll;J. Cooper;C. Marsden;A. Schapira
越来越多的证据表明，线粒体酶NADH辅酶Q还原酶(复合体I)的功能缺陷不仅与1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)毒性有关，而且与特发性帕金森病(PD)有关。复合型碘缺乏在帕金森病黑质中被发现，并且似乎是疾病特异性的，并且对中枢神经系统内的黑质具有选择性。我们描述了一种从60毫升血液中制备浓缩线粒体片段的方法。应用这项技术，我们分析了25例帕金森病患者和15名匹配的对照组的呼吸链功能。我们证实了先前关于帕金森病患者血小板线粒体中存在一种特殊的复合体I缺陷的报道。尽管PD组复合体I活性与对照组相比有统计学意义的降低(p=0.005)，但缺陷较轻(16%)；无法区分PD和对照组。这一缺陷在血小板全细胞匀浆中检测不到，可能反映了该制剂的相对不敏感性和PD患者复合体I活性的有限下降。在血小板中存在轻微的复合体I缺陷，同时在黑质中出现更严重的缺陷，这表明这两种组织的共同药理学特征使它们对一种或多种特定的毒素敏感，或者这种缺陷广泛分布，其他生化事件加剧了黑质的缺陷。
There is increasing evidence that defective function of the mitochondrial enzyme NADH CoQ reductase (complex I) is involved not only in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity, but also in idiopathic Parkinson's disease (PD). Complex I deficiency has been identified in PD substantia nigra and appears to be disease-specific and selective for the substantia nigra within the central nervous system. We describe a method for preparation of an enriched mitochondrial fraction from 60 mL blood. Using this technique, we analyzed respiratory chain function in 25 patients with PD and 15 matched control subjects. We confirm a previous report of a specific complex I deficiency in PD platelet mitochondria. Although there was a statistically significant decrease in complex I activity in the PD group compared with the control group (p = 0.005), the defect was mild (16%); it was not possible to distinguish PD from control values on an individual basis. This deficiency is not detectable in platelet whole-cell homogenates, presumably reflecting the relative insensitivity of this preparation and the limited decrease in complex I activity in PD. The presence of a mild complex I defect in platelets together with a more severe defect in substantia nigra suggests either that the pharmacological characteristics shared by these two tissues render them susceptible to a particular toxin or toxins, or that the defect is widely distributed and other biochemical events enhance the deficiency in substantia nigra.(ABSTRACT TRUNCATED AT 250 WORDS)