AMPK Inhibition Enhances the Neurotoxicity of Cu(II) in SH-SY5Y Cells

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• 作者：Ai-ping Lan ; Xian-jia Xiong ; Jun Chen ; Xi Wang ; Zhi-fang Chai…
• 关键词：Copper ; AMPK ; Apoptosis ; Neurotoxicity ; SH ; SY5Y
• 刊名：Neurotoxicity Research
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：30
• 期：3
• 页码：499-509
• 全文大小：3,196 KB
• 刊物主题：Neurosciences; Neurology; Neurochemistry; Pharmacology/Toxicology; Neurobiology; Cell Biology;
• 出版者：Springer US
• ISSN：1476-3524
• 卷排序：30

文摘

The involvement of copper in the pathophysiology of neurodegenerative disorders has been documented but remains poorly understood. This study aimed at investigating the molecular mechanism underlying copper-induced neurotoxicity. Human neuroblastoma SH-SY5Y cells were treated with different concentrations of Cu(II) (25–800 μM). The relative levels of AMPKα, phosphorylated (p)-AMPKα were examined by western blotting. The results showed that copper reduced cell viability and enhanced apoptosis of SH-SY5Y cells. Pretreatment with N-acetyl-l-cysteine, a common ROS scavenger, decreased copper-induced cytotoxicity. Furthermore, the levels of p-AMPKα in SH-SY5Y cells were increased by a relatively low concentration of copper and decreased by a relatively high concentration of copper at 24 h. Moreover, inhibition of AMPK with compound C or RNA interference aggravated concentration-dependent cytotoxicity of Cu(II). Taken together, these results indicated that AMPK activity might be important for the neurotoxicity of Cu(II).