Homocysteine potentiates β-amyloid neurotoxicity:: role of oxidative stress
Homocysteine potentiates β-amyloid neurotoxicity:: role of oxidative stress
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DOI：
10.1046/j.1471-4159.2001.00384.x
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发表时间：
2001-07-01
影响因子：
4.7
通讯作者：
Shea, TB
中科院分区：
文献类型：
--
作者：
Ho, PI;Collins, SC;Shea, TB
阿尔茨海默病 (AD) 神经元变性的原因尚未完全阐明，但有多种归因于胞质钙的增加和活性氧 (ROS) 生成的增加。淀粉样蛋白前体蛋白的β-淀粉样蛋白片段（Aβ）诱导钙内流、ROS 和细胞凋亡。同型半胱氨酸 (HC) 是一种神经毒性氨基酸，在 AD 等神经系统疾病中积累，也会诱导钙内流和氧化应激，已被证明会增强神经元兴奋性毒性，导致细胞凋亡。我们研究了 HC 可能增强 Aβ 神经毒性的可能性。 HG 增强了 Aβ 诱导的分化 SH-SY-5Y 人神经母细胞瘤细胞中胞质钙的增加和细胞凋亡。在与 HC 和 Aβ 共同处理后，抗氧化剂维生素 E 和谷胱甘肽前体 N-乙酰基-L-半胱氨酸可阻断细胞凋亡，表明细胞凋亡与氧化应激有关。这些发现强调，兴奋毒素在一定浓度下的适度积累（单独看来不会引发不良事件）可能会增强已知导致神经变性的其他因素（例如 Aβ）的影响。
The cause of neuronal degeneration in Alzheimer's disease (AD) has not been completely clarified, but has been variously attributed to increases in cytosolic calcium and increased generation of reactive oxygen species (ROS). The beta -amyloid fragment (A beta) of the amyloid precursor protein induces calcium influx, ROS and apoptosis. Homocysteine (HC), a neurotoxic amino acid that accumulates in neurological disorders including AD, also induces calcium influx and oxidative stress, which has been shown to enhance neuronal excitotoxicity, leading to apoptosis. We examined the possibility that HC may augment A beta neurotoxicity. HG potentiated the A beta -induced increase in Cytosolic calcium and apoptosis in differentiated SH-SY-5Y human neuroblastoma cells. The antioxidant vitamin E and the glutathione precursor N-acetyl-L-cysteine blocked apoptosis following cotreatment with HC and A beta, indicating that apoptosis is associated with oxidative stress. These findings underscore that moderate accumulation of excitotoxins at concentrations that alone do not appear to initiate adverse events may enhance the effects of other factors known to cause neurodegeneration such as A beta.