Recombinant human erythropoietin increases frataxin protein expression without increasing mRNA expression.
Friedreich's ataxia is an autosomal recessive neurodegenerative disease that is due to the loss of function of the frataxin protein. The molecular basis of this disease is still a matter of debate and treatments have so far focused on managing symptoms. Drugs that can increase the amount of frataxin protein offer a possible therapy for the disease. One such drug is recombinant human erythropoietin (rhu-EPO). Here, we report the effects of rhu-EPO on frataxin mRNA and protein in primary fibroblast cell cultures derived from Friedreich's ataxia patients. We observed a slight but significant increase in the amount of frataxin protein. Interestingly, we did not observe any increase in the messenger RNA expression at any of the times and doses tested, suggesting that the regulatory effects of rhu-EPO on the frataxin protein was at the post-translational level. These findings could help the evaluation of the treatment with erythropoietin as a potential therapeutic agent for Friedreich's ataxia.
Acquaviva
Fabio
F
Medical Genetics Unit, Department of Cellular and Molecular Biology, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy. fabio_h2o@hotmail.com
Castaldo
Imma
I
Filla
Alessandro
A
Giacchetti
Manuela
M
Marmolino
Daniele
D
Monticelli
Antonella
A
Pinelli
Michele
M
Saccà
Francesco
F
Cocozza
Sergio
S
D000328:Adult; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D005621:Friedreich Ataxia / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics*; D011994:Recombinant Proteins; D055815:Young Adult; D000096923:Frataxin
D004921:Erythropoietin; D033862:Iron-Binding Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000096923:Frataxin