title: Glutaredoxin 1 is a major player in copper metabolism in neuroblastoma cells.
abstract: BACKGROUND
  Glutaredoxin 1 (Grx1), a small protein belonging to the thioredoxin family, is involved in redox-regulation since it catalyzes the reduction of protein disulfides and that of mixed disulfides. It was reported to modulate active copper extrusion from cells, by affecting the function of the pumps ATP7A and B. These are components of the network of protein chaperones involved in the control of the homeostasis of copper, an essential, though harmful, metal. However, the effect of Grx1 on copper levels, copper chaperones and copper-elicited cell toxicity was never investigated.
  
  
  METHODS
  In order to investigate the effect of Grx1 on copper metabolism, we constitutively overexpressed Grx1 in human neuroblastoma SH-SY5Y cells (SH-Grx1 cells) and assessed a number of copper-related parameters.
  
  
  RESULTS
  SH-Grx1 cells show a basal intracellular copper level higher than control cells, accumulate more copper upon CuSO4 treatment, but are more resistant to copper-induced toxicity. Grx1 shows copper-binding properties and copper overload produces a decrease of Grx1 enzyme activity in SH-Grx1 cells. Finally, Grx1 overexpression decreases copper accumulation in mitochondria upon copper overload and modulates the expression of copper transporter 1 (Ctr1).
  
  
  CONCLUSIONS
  Altogether, these data demonstrate that Grx1 is a major player in copper metabolism in neuronal cells.
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Italy.
authors.forename: Maria Lisa
authors.initials: ML
authors.lastname: De Benedetto
authors.forename: Concetta Rosa
authors.initials: CR
authors.lastname: Capo
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferri
authors.forename: Cristiana
authors.initials: C
authors.lastname: Valle
authors.forename: Renato
authors.initials: R
authors.lastname: Polimanti
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Carrì
authors.forename: Luisa
authors.initials: L
authors.lastname: Rossi
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002846:Chromatography, Affinity; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014407:Tumor Cells, Cultured
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D054477:Glutaredoxins; D012333:RNA, Messenger; C000606290:SOD1 protein, human; D003300:Copper; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione
keywords: Copper; Ctr1; Grx1; SH-SY5Y