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

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 mu M). The relative levels of AMPK alpha, phosphorylated (p)-AMPK alpha 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-AMPK alpha 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).