Lan Ai-Ping, Xiong Xian-Jia, Chen Jun, Wang Xi, Chai Zhi-Fang, Hu Yi
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.
Department of Physiology, School of Medicine, Tianjin Medical University, Tianjin, 300070, China.
Neurotox Res. 2016 Oct;30(3):499-509. doi: 10.1007/s12640-016-9651-3. Epub 2016 Jul 19.
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).
铜参与神经退行性疾病的病理生理过程已有文献记载，但仍了解甚少。本研究旨在探究铜诱导神经毒性的分子机制。用不同浓度的Cu(II)（25 - 800 μM）处理人神经母细胞瘤SH - SY5Y细胞。通过蛋白质免疫印迹法检测AMPKα、磷酸化（p）-AMPKα的相对水平。结果表明，铜降低了SH - SY5Y细胞的活力并增强了其凋亡。用常见的活性氧清除剂N - 乙酰 - L - 半胱氨酸预处理可降低铜诱导的细胞毒性。此外，在24小时时，相对低浓度的铜可增加SH - SY5Y细胞中p - AMPKα的水平，而相对高浓度的铜则使其降低。此外，用化合物C抑制AMPK或RNA干扰会加重Cu(II)的浓度依赖性细胞毒性。综上所述，这些结果表明AMPK活性可能对Cu(II)的神经毒性很重要。
