Krapfenbauer Kurt, Engidawork Ephrem, Cairns Nigel, Fountoulakis Michael, Lubec Gert
F. Hoffman-La Roche, Basel, Switzerland.
Brain Res. 2003 Mar 28;967(1-2):152-60. doi: 10.1016/s0006-8993(02)04243-9.
An increasing body of evidence indicates that oxidative stress and damage play a role in the pathogenesis of a number of diseases associated with neurodegeneration, including Down syndrome (DS), Alzheimer's disease (AD) and Pick's disease (PD). Although oxidative stress is a common element in these diseases, specific clinico-pathological phenotypes have been described for each disorder. Development of these phenotypes might be linked, among others, to differences in antioxidant response. The present study is designed to investigate expression of peroxiredoxins (Prxs), the newly characterized family of highly conserved antioxidant enzymes, and other antioxidant enzymes in frontal cortex and cerebellum of DS, AD and PD patients using the technique of proteomics. Levels of Prx I, Mn superoxide dismutase (SOD2) and glutathione-S-transferase omega1 in DS, AD and PD were not significantly different from that of controls in both brain regions investigated. In contrast, Prx II was significantly increased (P<0.05) in frontal cortex of DS, AD and PD, whereas Prx III was decreased in frontal cortex of DS (P<0.01) and PD (P<0.001). Interestingly, Prx VI displayed a significant increase (P<0.05) only in PD frontal cortex. The present data indicate that differential regulation of antioxidant enzymes exist in DS, AD and PD, suggestive of the diversity as well as distinct functional roles of these proteins. Moreover, while up-regulation of Prx II appears to provide evidence for the existence of compensatory response in increased cell loss, up-regulation of Prx VI may be used to discriminate PD from AD as well as DS.
越来越多的证据表明，氧化应激和损伤在包括唐氏综合征（DS）、阿尔茨海默病（AD）和匹克病（PD）在内的多种与神经退行性变相关疾病的发病机制中起作用。尽管氧化应激是这些疾病的一个共同因素，但每种疾病都有特定的临床病理表型。这些表型的发展可能与抗氧化反应的差异等因素有关。本研究旨在利用蛋白质组学技术研究过氧化物还原酶（Prxs）（新发现的高度保守的抗氧化酶家族）以及其他抗氧化酶在DS、AD和PD患者额叶皮质和小脑中的表达。在研究的两个脑区中，DS、AD和PD患者的Prx I、锰超氧化物歧化酶（SOD2）和谷胱甘肽-S-转移酶ω1水平与对照组相比无显著差异。相比之下，DS、AD和PD患者额叶皮质中的Prx II显著增加（P<0.05），而DS（P<0.01）和PD（P<0.001）患者额叶皮质中的Prx III则降低。有趣的是，Prx VI仅在PD额叶皮质中显著增加（P<0.05）。目前的数据表明，DS、AD和PD中存在抗氧化酶的差异调节，提示这些蛋白质具有多样性以及不同的功能作用。此外，虽然Prx II的上调似乎为细胞损失增加时存在代偿反应提供了证据，但Prx VI的上调可用于区分PD与AD以及DS。
