Recombinant human erythropoietin: effects on frataxin expression in vitro.
BACKGROUND
Friedreich's ataxia (FRDA) is a neurodegenerative disorder caused by decreased expression of the protein frataxin, recently described to be an iron chaperone for the assembly of iron-sulphur clusters in the mitochondria, causing iron accumulation in mitochondria, oxidative stress and cell damage. Searching for compounds that could possibly influence frataxin expression, we found that the cytokine recombinant human erythropoietin (rhuEPO) significantly increases frataxin expression by a still unknown mechanism.


METHODS
Isolated lymphocytes from FRDA patients, isolated human cardiac cells (fibroblasts and myocytes) from patients undergoing heart transplantation and P19 mouse cells (neuronal typ), were incubated with different concentrations of rhuEPO, and immunoblot was carried out for the detection of frataxin.


RESULTS
We show for the first time that the cytokine recombinant human erythropoietin (rhuEPO) can, additionally to its reported neuro- and cardioprotective properties, increase frataxin expression in vitro. We show that rhuEPO significantly increases frataxin expression in primary lymphocytes from patients with Friedreich's ataxia. Further we show that rhuEPO can also increase frataxin expression in many other cell types; among them the most affected cell types in FRDA such as neurones and cardiac cells.


CONCLUSIONS
Our results provide a scientific basis for further studies examining the effectiveness of this agent for the treatment of FRDA patients.
Sturm
B
B
Medical University of Vienna, Vienna, Austria.
Stupphann
D
D
Kaun
C
C
Boesch
S
S
Schranzhofer
M
M
Wojta
J
J
Goldenberg
H
H
Scheiber-Mojdehkar
B
B
D002460:Cell Line; D002478:Cells, Cultured; D004921:Erythropoietin / Q000627:therapeutic use*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005621:Friedreich Ataxia / Q000188:drug therapy*; D006801:Humans; D033862:Iron-Binding Proteins / Q000032:analysis*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins; D000096923:Frataxin
D004921:Erythropoietin; D033862:Iron-Binding Proteins; D011994:Recombinant Proteins; D000096923:Frataxin