Acetaldehyde Induces Cytotoxicity of SH-SY5Y Cells via Inhibition of Akt Activation and Induction of Oxidative Stress.
Acetaldehyde Induces Cytotoxicity of SH-SY5Y Cells via Inhibition of Akt Activation and Induction of Oxidative Stress.
复制标题
乙醛通过抑制 Akt 激活和诱导氧化应激诱导 SH-SY5Y 细胞的细胞毒性
DOI：
10.1155/2016/4512309
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发表时间：
2016
影响因子：
--
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Yan T;Zhao Y;Zhang X
过量饮酒会导致脑组织损伤和认知功能障碍。研究表明，大量饮酒与阿尔茨海默病等神经退行性疾病的早期发病有关。乙醛是乙醇毒性最强的代谢产物，推测其介导慢性过量饮酒引起的脑组织损伤和认知功能障碍。然而，乙醛诱导神经毒性的确切机制还不完全清楚。本研究观察了乙醛对SH-SY 5 Y细胞的细胞毒作用，发现乙醛通过下调抗凋亡基因Bcl-2和Bcl-xL的表达，上调促凋亡基因Bax的表达，诱导SH-SY 5 Y细胞凋亡。乙醛处理导致活化Akt和环AMP反应元件结合蛋白（CREB）的水平显着下降。此外，乙醛诱导p38丝裂原活化蛋白激酶（MAPK）的激活，同时抑制细胞外信号调节激酶（ERK，p44/p42 MAPK）的激活。同时，乙醛处理引起的活性氧的产生增加，并在SH-SY 5 Y细胞的氧化应激。因此，乙醛通过促进凋亡信号传导、抑制细胞存活途径和诱导氧化应激诱导SH-SY 5 Y细胞的细胞毒性。
Excessive alcohol consumption can lead to brain tissue damage and cognitive dysfunction. It has been shown that heavy drinking is associated with an earlier onset of neurodegenerative diseases such as Alzheimer's disease. Acetaldehyde, the most toxic metabolite of ethanol, is speculated to mediate the brain tissue damage and cognitive dysfunction induced by the chronic excessive consumption of alcohol. However, the exact mechanisms by which acetaldehyde induces neurotoxicity are not totally understood. In this study, we investigated the cytotoxic effects of acetaldehyde in SH-SY5Y cells and found that acetaldehyde induced apoptosis of SH-SY5Y cells by downregulating the expression of antiapoptotic Bcl-2 and Bcl-xL and upregulating the expression of proapoptotic Bax. Acetaldehyde treatment led to a significant decrease in the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB). In addition, acetaldehyde induced the activation of p38 mitogen-activated protein kinase (MAPK) while inhibiting the activation of extracellular signal-regulated kinases (ERKs, p44/p42MAPK). Meanwhile, acetaldehyde treatment caused an increase in the production of reactive oxygen species and elevated the oxidative stress in SH-SY5Y cells. Therefore, acetaldehyde induces cytotoxicity of SH-SY5Y cells via promotion of apoptotic signaling, inhibition of cell survival pathway, and induction of oxidative stress.