AMPK Inhibition Enhances the Neurotoxicity of Cu(II) in SH-SY5Y Cells
Ai-Ping Lan1, Xian-Jia Xiong1,2, Jun Chen1
1CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Multi-disciplinary Research Division, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, 100049, China.
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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).
