4-Hydroxynonenal Induces Mitochondrial-Mediated Apoptosis and Oxidative Stress in SH-SY5Y Human Neuronal Cells
4-Hydroxynonenal Induces Mitochondrial-Mediated Apoptosis and Oxidative Stress in SH-SY5Y Human Neuronal Cells
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DOI：
10.1111/j.1742-7843.2011.00834.x
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发表时间：
2012-05-01
影响因子：
3.1
通讯作者：
Farombi, Ebenezer O.
中科院分区：
文献类型：
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作者：
Abarikwu, Sunny O.;Pant, Aditya B.;Farombi, Ebenezer O.
氧化应激和细胞凋亡的过度和持续增加与许多疾病的发病机制有关。在这项研究中，我们证明了4-羟基壬烯醛（4-HNE），一种在一定浓度范围内（0.150 μ M）的脂质过氧化产物，在暴露4小时时浓度>5 μ M时对SH-SY 5 Y细胞培养物显示出细胞毒性作用。4-HNE剂量依赖性地降低细胞活力，并显着促进活性氧形成和增强氧化应激，反映在脂质过氧化和过氧化氢酶活性水平的增加和谷胱甘肽过氧化物酶活性以及谷胱甘肽水平的降低。4-HNE诱导的氧化应激与SH-SY 5 Y细胞中Bax和p53的转录和翻译表达增加相关。线粒体介导的凋亡被证实的caspase-3的表达和活性增加。我们的数据表明，4-HNE诱导神经细胞死亡，通过异常表达的凋亡标志物（p53，Bax和caspase-3）。氧化应激可能参与SH-SY 5 Y细胞对4-HNE诱导的体外细胞毒性的初始引发。
Excessive and sustained increases in oxidative stress and apoptosis have been implicated in the pathogenesis of many diseases. In this study, we demonstrated that 4-hydroxynonenal (4-HNE), a product of lipid peroxidation in a range of concentration (0.150 mu M) showed cytotoxic effects on SH-SY5Y cell culture at a concentration >5 mu M at 4 hr of exposure. 4-HNE dose dependently decreased cell viability and significantly promoted reactive oxygen species formation and enhanced oxidative stress as reflected in the increased level of lipid peroxidation and catalase activity and decreased glutathione peroxidase activity as well as glutathione levels. 4-HNE-induced oxidative stress was associated with increased transcriptional and translational expressions of Bax and p53 in SH-SY5Y cells. Mitochondrial-mediated apoptosis was confirmed by increased expression and activity of caspase-3. Our data demonstrate that 4-HNE induces neuronal cell death through abnormal expression of apoptotic markers (p53, Bax and caspase-3). Oxidative stress may be involved in the initial priming of SH-SY5Y cells to 4-HNE-induced cytotoxicity in vitro.