Oxidative stress and reduced antioxidant defenses in peripheral cells from familial Alzheimer's patients.
Oxidative stress and reduced antioxidant defenses in peripheral cells from familial Alzheimer's patients.
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DOI：
10.1016/s0891-5849(02)01049-3
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发表时间：
2002-11-15
影响因子：
7.4
通讯作者：
Liguri, Gianfranco
中科院分区：
文献类型：
--
作者：
Cecchi, Cristina;Fiorillo, Claudia;Liguri, Gianfranco
我们已经测量了典型的脂质过氧化，蛋白质氧化和总抗氧化能力（TAC）的过程中的最终产品的水平，在皮肤成纤维细胞和淋巴母细胞从家族性阿尔茨海默病（FAD），散发性阿尔茨海默病（AD），和年龄匹配的健康对照患者。与对照组相比，携带淀粉样前体蛋白（APP）和早老素-1（PS-1）基因突变的成纤维细胞和成淋巴细胞的脂质过氧化产物、丙二醛（MDA）和4-羟基壬烯醛（4-HNE）明显增加。相反，FAD患者细胞的抗氧化防御能力低于正常人。淋巴母细胞中的脂质过氧化和抗氧化能力，从散发性AD患者的正常对照组的基础值几乎没有区别。对蛋白质的氧化攻击导致FAD患者的蛋白质羰基含量高于年龄匹配的对照组。此外，ADP核糖基化水平的聚（ADP-核糖）聚合酶（PARP）核底物显着提高，而PARP含量没有显着差异携带基因突变的成纤维细胞和对照细胞。这些结果表明，携带APP和PS-1基因突变的外周细胞显示氧化标记物水平的改变，即使它们不直接参与AD的神经退行性过程。这些结果支持了这样的假设，即脂质，蛋白质和DNA的氧化损伤是AD发病机制中的重要早期事件。
We have measured the levels of typical end products of the processes of lipid peroxidation, protein oxidation, and total antioxidant capacity (TAC) in skin fibroblasts and lymphoblasts taken from patients with familial Alzheimer's disease (FAD), sporadic Alzheimer's disease (AD), and age-matched healthy controls. Compared to controls, the fibroblasts and lymphoblasts carrying amyloid precursor protein (APP) and presenilin-1 (PS-1) gene mutations showed a clear increase in lipoperoxidation products, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE). In contrast, the antioxidant defenses of cells from FAD patients were lower than those from normal subjects. Lipoperoxidation and antioxidant capacity in lymphoblasts from patients affected by sporadic AD were virtually indistinguishable from the basal values of normal controls. An oxidative attack on protein gave rise to greater protein carbonyl content in FAD patients than in age-matched controls. Furthermore, ADP ribosylation levels of poly(ADP-ribose) polymerase (PARP) nuclear substrates were significantly raised, whereas the PARP content did not differ significantly between fibroblasts carrying gene mutations and control cells. These results indicate that peripheral cells carrying APP and PS-1 gene mutations show altered levels of oxidative markers even though they are not directly involved in the neurodegenerative process of AD. These results support the hypothesis that oxidative damage to lipid, protein, and DNA is an important early event in the pathogenesis of AD.