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

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Abstract

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).

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grant Nos. 11375213 and 21390411) and Hundred Talents Program of the Chinese Academy of Sciences.

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Authors and Affiliations

  1. CAS 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

    Ai-ping Lan, Xian-jia Xiong, Jun Chen, Zhi-fang Chai & Yi Hu

  2. Department of Physiology, School of Medicine, Tianjin Medical University, Tianjin, 300070, China

    Xian-jia Xiong & Xi Wang

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  1. Ai-ping Lan
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  2. Xian-jia Xiong
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Correspondence to Yi Hu.

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Lan, Ap., Xiong, Xj., Chen, J. et al. AMPK Inhibition Enhances the Neurotoxicity of Cu(II) in SH-SY5Y Cells. Neurotox Res 30, 499–509 (2016). https://doi.org/10.1007/s12640-016-9651-3

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  • DOI: https://doi.org/10.1007/s12640-016-9651-3

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