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- Title
Carbamylated erythropoietin increases frataxin independent from the erythropoietin receptor.
- Authors
Sturm, Brigitte; Helminger, Melissa; Steinkellner, Hannes; Heidari, Mohammad Mehdi; Goldenberg, Hans; Scheiber-Mojdehkar, Barbara
- Abstract
Eur J Clin Invest 2010; 40 (6): 561–565 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.
- Subjects
NEURODEGENERATION; ERYTHROPOIETIN; FRATAXIN; LYMPHOCYTES; ENZYME-linked immunosorbent assay
- Publication
European Journal of Clinical Investigation, 2010, Vol 40, Issue 6, p561
- ISSN
0014-2972
- Publication type
Article
- DOI
10.1111/j.1365-2362.2010.02292.x