title: Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level.
abstract: OBJECTIVE
  Copper is an essential trace element that serves as an important catalytic cofactor for cuproenzymes, carrying out major biological functions in growth and development. Although Wilson's disease (WD) is unquestionably caused by mutations in the ATP7B gene and subsequent copper overload, the precise role of copper in inducing pathological changes remains poorly understood.
  
  
  METHODS
  Our study aimed to explore, in HepG2 cells exposed to copper, the cell viability and apoptotic cells was tested by MTT and Hoechst 33342 stainning respectively, and the signaling pathways involved in oxidative stress response, apoptosis and lipid metabolism were determined by real time RT-PCR and Western blot analysis.
  
  
  RESULTS
  The results demonstrate dose- and time-dependent cell viability and apoptosis in HepG2 cells following treatment with 10 μM, 200 μM and 500 μM of copper sulfate for 8 and 24 h. Copper overload significantly induced the expression of HSPA1A (heat shock 70 kDa protein 1A), an oxidative stress-responsive signal gene, and BAG3 (BCL2 associated athanogene3), an anti-apoptotic gene, while expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), a lipid biosynthesis and lipid metabolism gene, was inhibited.
  
  
  CONCLUSIONS
  These findings provide new insights into possible mechanisms accounting for the development of liver apoptosis and steatosis in the early stages of Wilson's disease.
authors.affiliation: Department of Anesthesiology, Tumor Hospital Xiangya School of Medicine of Central South University, Changsha, China. fishgugu@sina.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Huarong
authors.initials: H
authors.lastname: Yang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Song
authors.forename: Shaojuan
authors.initials: S
authors.lastname: Gu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D019327:Copper Sulfate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D018840:HSP70 Heat-Shock Proteins; C490786:HSPA1A protein, human; D012333:RNA, Messenger; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; D019327:Copper Sulfate