Amyloid-β-Peptide Reduces the Expression Level of Mitochondrial Cytochrome Oxidase Subunits
Amyloid-β-Peptide Reduces the Expression Level of Mitochondrial Cytochrome Oxidase Subunits
复制标题
淀粉样蛋白-β-肽降低线粒体细胞色素氧化酶亚基的表达水平
作者：
W. K. Hong;E. Han;D. Kim;J. Ahn;J. Park;B. Han
线粒体功能障碍是包括阿尔茨海默病（AD）在内的神经系统疾病的重要原因。线粒体在活性氧 (ROS) 的产生中发挥着关键作用，导致 AD 大脑中神经元细胞和细胞区室的氧化损伤。 β 淀粉样蛋白 (Aβ) 是淀粉样斑块中由 25-35 个氨基酸组成的蛋白质片段，其诱导的细胞毒性已被证明具有神经毒性特性。它们似乎涉及线粒体功能障碍，但其潜在机制尚不清楚。本研究的目的是评估 Aβ 诱导的线粒体功能障碍是否涉及细胞色素 C 氧化酶 (COX) 表达的变化。我们测量了 SK-N-SH 细胞（人类神经母细胞瘤细胞系）暴露于 Aβ 后 COX 的活性。我们发现，在 Aβ 处理的 SK-N-SH 细胞中，表达线粒体 COX 亚基的 mRNA 水平以剂量依赖性方式显着降低。 Aβ 治疗后，人线粒体转录因子 1 (TFAM) mRNA 水平也下降。这些结果表明 Aβ 通过减少 TFAM 来调节线粒体基因表达。
Mitochondrial dysfunction is an important cause of neurological disorder including Alzheimer’s disease (AD). Mitochondria play a key role in the generation of reactive oxygen species (ROS), resulting in oxidative damage to neuronal cell and cellular compartments in the AD brain. Cytotoxicity induced by amyloid-beta (Aβ), a protein fragment of 25–35 amino acids in amyloid plaques has been shown to have neuro-toxic properties. They seem to involve mitochondrial dysfunction, but the underlying mechanisms are not clearly understood. The purpose of this study was to assess whether Aβ induced mitochondrial dysfunction involves changes in cytochrome c oxidase (COX) expression. We measured the activities of COX after expose of SK-N-SH cells (a human neuroblastoma cell line) to Aβ. We found that levels of mRNAs expressing mitochondrial COX subunits decreased significantly in Aβ-treated SK-N-SH cells in a dose-dependent manner. Human mitochondrial transcription factor-1 (TFAM) mRNA level also decreased after Aβ-treatment. These results suggest that Aβ modulates the mitochondrial gene expression through a decrease in TFAM.
影响因子：
7.4
作者：
Hensley, K;Robinson, KA;Floyd, RA
通讯作者：
Floyd, RA
影响因子：
56.9
作者：
YANKNER, BA;DAWES, LR;NEVE, RL
通讯作者：
NEVE, RL