Carbamylated erythropoietin increases frataxin independent from the erythropoietin receptor.
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.
Sturm
Brigitte
B
Medical University of Vienna, Vienna, Austria.
Helminger
Melissa
M
Steinkellner
Hannes
H
Heidari
Mohammad Mehdi
MM
Goldenberg
Hans
H
Scheiber-Mojdehkar
Barbara
B
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
D004921:Erythropoietin; D033862:Iron-Binding Proteins; D011994:Recombinant Proteins; D000096923:Frataxin; C488171:carbamylated erythropoietin