Protective effects of vitamin E against oxidative damage induced by Aβ1-40Cu(II) complexes
Protective effects of vitamin E against oxidative damage induced by Aβ1-40Cu(II) complexes
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DOI：
10.1111/j.1745-7270.2007.00261.x
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发表时间：
2007-02-01
影响因子：
3.7
通讯作者：
Jiang, Zhaofeng
中科院分区：
文献类型：
--
作者：
Dai, Xueling;Sun, Yaxuan;Jiang, Zhaofeng
β-淀粉样肽（A β）被认为是老年斑形成的原因，老年斑是阿尔茨海默病（AD）的标志。氧化应激，表现为蛋白质氧化和脂质过氧化，以及其他改变，是AD脑的特征。越来越多的证据支持Ap（1-40）形成在CuZn超氧化物歧化酶样结合位点结合铜的寡聚复合物。β Cu 1 -40（II）配合物通过Cu 2+还原从O-2产生神经毒性过氧化氢（H2 O2），尽管精确的反应机制尚不清楚。当以100 μ M的浓度加入（+）-α-生育酚（维生素E）作为自由基抗氧化剂时，Ap（1-40）或Ap（1-40）Cu（II）络合物对培养的原代皮层神经元的毒性部分减弱。来自乳酸脱氢酶（LDH）释放和H2 O2形成的数据证实了MTT试验的结果。这些发现表明，铜与A β（1-40）的结合可导致H2 O2的产生增加，从而导致质膜完整性的破坏和随后的神经元死亡。用维生素E治疗的组表现出轻微得多的损伤，这表明维生素E在保护神经元细胞免受功能障碍或死亡方面起着关键作用。
beta-amyloid peptide (A beta) is considered to be responsible for the formation of senile plaques, which is the hallmark of Alzheimer's disease (AD). Oxidative stress, manifested by protein oxidation and lipid peroxidation, among other alterations, is a characteristic of AD brain. A growing body of evidence has been presented in support of Ap(1-40) forming an oligomeric complex that binds copper at a CuZn superoxide dismutase-like binding site. A beta Cu1-40(II) complexes generate neurotoxic hydrogen peroxide (H2O2) from O-2 via Cu2+ reduction, though the precise reaction mechanism is unclear. The toxicity of Ap(1-40) or the Ap(1-40)Cu(II) complexes to cultured primary cortical neurons was partially attenuated when (+)-alpha-tocopherol (vitamin E) as free radical antioxidant was added at a concentration of 100 mu M. The data derived from lactate dehydrogenase (LDH) release and the formation of H2O2 confirmed the results from the MTT assay. These findings indicate that copper binding to A beta(1-40) can give rise to greater production of H2O2, which leads to a breakdown in the integrity of the plasma membrane and subsequent neuronal death. Groups treated with vitamin E exhibited much slighter damage, suggesting that vitamin E plays a key role in protecting neuronal cells from dysfunction or death.