title: Carbamylated erythropoietin increases frataxin independent from the erythropoietin receptor.
abstract: BACKGROUND
  Friedreich's ataxia (FRDA) is a neurodegenerative disorder caused by decreased expression of the mitochondrial protein frataxin. Recently we showed in a clinical pilot study in Friedreich's ataxia patients that recombinant human erythropoietin (rhuEPO) significantly increases frataxin-expression. In this in vitro study, we investigated the role of the erythropoietin receptor (EPO-R) in the frataxin increasing effect of rhuEPO and if nonerythropoietic carbamylated erythropoietin (CEPO), which cannot bind to the classical EPO-R increases frataxin expression.
  
  
  METHODS
  In our experiments human erythroleukaemic K562 cells (+ EPO-R), human monocytic leukemia THP-1 cells (- EPO-R) and isolated primary lymphocytes from healthy control and FRDA patients were incubated with different concentrations of rhuEPO or CEPO. Frataxin-expression was detected by an electrochemical luminescence immunoassay (based on the principle of an ELISA).
  
  
  RESULTS
  We show that rhuEPO increases frataxin-expression in K562 cells (expressing EPO-R) as well as in THP-1 cells (without EPO-R expression). These results were confirmed by the finding that CEPO, which cannot bind to the classical EPO-R increased frataxin expression in the same concentration range as rhuEPO. In addition, we show that both EPO derivatives significantly increase frataxin-expression in vitro in control and Friedreich's ataxia patients primary lymphocytes.
  
  
  CONCLUSIONS
  Our results provide a scientific basis for further studies examining the effectiveness of nonerythropoietic derivatives of erythropoietin for the treatment of Friedreich's ataxia patients.
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sturm
authors.forename: Melissa
authors.initials: M
authors.lastname: Helminger
authors.forename: Hannes
authors.initials: H
authors.lastname: Steinkellner
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Heidari
authors.forename: Hans
authors.initials: H
authors.lastname: Goldenberg
authors.forename: Barbara
authors.initials: B
authors.lastname: Scheiber-Mojdehkar
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004921:Erythropoietin / Q000031:analogs & derivatives / Q000494:pharmacology*; D005621:Friedreich Ataxia / Q000188:drug therapy*; D006801:Humans; D033862:Iron-Binding Proteins / Q000032:analysis*; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D000096923:Frataxin
chemical_list: D004921:Erythropoietin; D033862:Iron-Binding Proteins; D011994:Recombinant Proteins; D000096923:Frataxin; C488171:carbamylated erythropoietin