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Carbamylated erythropoietin increases frataxin independent from the erythropoietin receptor
Author(s) -
Sturm Brigitte,
Helminger Melissa,
Steinkellner Hannes,
Heidari Mohammad Mehdi,
Goldenberg Hans,
ScheiberMojdehkar Barbara
Publication year - 2010
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2010.02292.x
Subject(s) - frataxin , erythropoietin , ataxia , erythropoietin receptor , in vitro , endocrinology , medicine , chemistry , microbiology and biotechnology , iron binding proteins , biochemistry , biology , transferrin , psychiatry
Eur J Clin Invest 2010; 40 (6): 561–565 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. Materials and 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. Conclusion 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.