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The reduction of NADH Ubiquinone oxidoreductase 24-and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer's disease

机译:唐氏综合症和阿尔茨海默氏病患者脑中NADH泛醌氧化还原酶24和75 kDa亚基的减少

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NADH: ubiquinone oxidoreductase (complex I), one of the most complicated multi-protein enzyme complexes, is important for energy metabolism because it is the initial enzyme of the mitochondrial respiratory chain. Deficiency of complex I is frequently found in various tissues of patients with neurodegenerative disease. Here we studied the protein levels of complex I 24- and 75-kDa subunits in several brain regions from patients with Down syndrome (DS) and Alzheimer's disease (AD). We determined protein levels of complex I 24-, 75-kDa subunits and mitochondrial marker proteins mitochondrial matrix protein P1 (hsp60) and aconitate hydratase from seven brain regions of patients with DS, AD and controls. Proteins were separated by two-dimensional (2-D) gel electrophoresis and identified by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). Complex I 24-kDa subunit was significantly reduced in occipital cortex and thalamus in patients with DS and temporal and occipital cortices in patients with AD. Complex I 75-kDa subunit was significantly reduced in brain regions from patients with DS (temporal, occipital and caudate nucleus) and AD (parietal cortex). Reductions of two subunits of complex I may lead to the impairment of energy metabolism and result in neuronal cell death (apoptosis), a hallmark of both neurodegenerative disorders. (C) 2001 Elsevier Science Inc. All rights reserved. [References: 36]
机译:NADH:泛醌氧化还原酶(复合物I),最复杂的多蛋白酶复合物之一,对能量代谢很重要,因为它是线粒体呼吸链的初始酶。在神经退行性疾病患者的各种组织中经常发现复合物I的缺乏。在这里,我们研究了唐氏综合症(DS)和阿尔茨海默氏病(AD)患者在多个大脑区域中复杂的I 24-和75-kDa亚基的蛋白质水平。我们确定了DS,AD和对照患者的七个大脑区域中复杂的I 24-,75-kDa亚基的蛋白质水平以及线粒体标记蛋白线粒体基质蛋白P1(hsp60)和乌头水合酶。通过二维(2-D)凝胶电泳分离蛋白质,并通过基质辅助激光解吸电离质谱(MALDI-MS)进行鉴定。 DS患者的枕叶皮质和丘脑复合物I复合物24 kDa亚基显着降低,AD患者的颞枕叶皮质显着降低。 DS(颞,枕和尾状核)和AD(顶叶皮质)患者的脑区域复合物I 75-kDa亚基显着减少。复合物I的两个亚基的还原可能导致能量代谢受损,并导致神经元细胞死亡(凋亡),这是两种神经退行性疾病的标志。 (C)2001 Elsevier Science Inc.保留所有权利。 [参考:36]

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