The reduction of NADH Ubiquinone oxidoreductase 24-and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer's disease
The reduction of NADH Ubiquinone oxidoreductase 24-and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer's disease
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DOI：
10.1016/s0024-3205(01)01074-8
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发表时间：
2001-05-04
期刊：
影响因子：
6.1
通讯作者：
Lubec, G
中科院分区：
文献类型：
--
作者：
Kim, SH;Vlkolinsky, R;Lubec, G
NADH：泛醌氧化还原酶（复合物I）是最复杂的多蛋白酶复合物之一，对于能量代谢是重要的，因为它是线粒体呼吸链的起始酶。复合物I的缺乏经常在患有神经退行性疾病的患者的各种组织中发现。在这里，我们研究了蛋白质水平的复合物I 24-和75-kDa亚基在几个脑区唐氏综合征（DS）和阿尔茨海默病（AD）患者。我们确定了蛋白质水平的复合物I 24-，75-kDa的亚基和线粒体标记蛋白线粒体基质蛋白P1（HSP 60）和乌头酸水合酶从7个脑区的患者DS，AD和控制。蛋白质通过二维（2-D）凝胶电泳进行分离，并通过基质辅助激光解吸电离质谱（MALDI-MS）进行鉴定。复合物I 24-kDa亚单位显着减少，在枕叶皮质和丘脑患者DS和颞叶和枕叶皮质AD患者。复合物I 75-kDa亚基显着减少，从DS（颞，枕和尾状核）和AD（顶叶皮质）患者的大脑区域。复合物I的两个亚基的减少可导致能量代谢的损伤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. All rights reserved.
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.