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. MATERIALS AND 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.
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 humanerythropoietin (rhuEPO) significantly increases frataxin expression by a still unknown mechanism. MATERIALS AND METHODS: Isolated lymphocytes from FRDApatients, 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 humanerythropoietin (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 FRDApatients.
Authors: Giovanni Coppola; Ryan Burnett; Susan Perlman; Revital Versano; Fuying Gao; Heather Plasterer; Myriam Rai; Francesco Saccá; Alessandro Filla; David R Lynch; James R Rusche; Joel M Gottesfeld; Massimo Pandolfo; Daniel H Geschwind Journal: Ann Neurol Date: 2011-11 Impact factor: 10.422
Authors: Tanya V Aranca; Tracy M Jones; Jessica D Shaw; Joseph S Staffetti; Tetsuo Ashizawa; Sheng-Han Kuo; Brent L Fogel; George R Wilmot; Susan L Perlman; Chiadi U Onyike; Sarah H Ying; Theresa A Zesiewicz Journal: Neurodegener Dis Manag Date: 2016
Authors: Ngolela E Babady; Nadege Carelle; Robert D Wells; Tracey A Rouault; Michio Hirano; David R Lynch; Martin B Delatycki; Robert B Wilson; Grazia Isaya; Hélène Puccio Journal: Mol Genet Metab Date: 2007-06-26 Impact factor: 4.797
Authors: Karl Egger; Christian Clemm von Hohenberg; Michael F Schocke; Charles R G Guttmann; Demian Wassermann; Marlene C Wigand; Wolfgang Nachbauer; Christian Kremser; Brigitte Sturm; Barbara Scheiber-Mojdehkar; Marek Kubicki; Martha E Shenton; Sylvia Boesch Journal: J Neuroimaging Date: 2013-09-09 Impact factor: 2.486