title: AMPK Inhibition Enhances the Neurotoxicity of Cu(II) in SH-SY5Y Cells.
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).
authors.affiliation: 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.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Lan
authors.affiliation: 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.
authors.forename: Xian-Jia
authors.initials: XJ
authors.lastname: Xiong
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Physiology, School of Medicine, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Chai
authors.affiliation: 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. huyi@ihep.ac.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003300:Copper / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D003300:Copper; D055372:AMP-Activated Protein Kinases; D000111:Acetylcysteine
keywords: AMPK; Apoptosis; Copper; Neurotoxicity; SH-SY5Y