title: Erythropoietin enhances cell proliferation and survival of human fetal neuronal progenitors in normoxia.
abstract: Extensive data reporting the neurogenerative, neuroprotective and neuroregenerative potential of erythropoietin (EPO), mainly on RNA level, can be found in the literature. However, there is still a poor knowledge on the response of neuronal progenitor cells (NPC) upon stimulation with EPO in terms of the protein species involved. Herein, the effect of EPO on the proliferation of human mesencephalic NPC (hmNPC) under normoxia is monitored using cellular assays and proteomic analysis (two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry). The administration of EPO increased the proliferation of hmNPC within 4 days after application. It positively influenced the cell-cycle progression by affecting the G2 phase of the cell cycle. A proteomic analysis of the protein expression in hmNPC cultures 4 days after EPO treatment identified 8 proteins differentially expressed in EPO-treated cultures. It is likely that one or more of the identified proteins are involved in cellular pathways that promote cell proliferation and differentiation of hmNPC under normoxia. Their further characterization could provide cellular targets for the development of new therapeutic agents to treat CNS injury. Moreover, as EPO signaling is hypoxia-inducible, our findings may also indicate the beneficial effect of EPO to mimic hypoxia, while bypassing its negative effects, to culture human fetal midbrain-derived progenitor cells.
authors.affiliation: Department of Cell Technologies and Applied Stem Cell Biology, Biomedical-Biotechnological Centre, University of Leipzig, Leipzig, Germany. sanja.pavlica@bbz.uni-leipzig.de
authors.forename: Sanja
authors.initials: S
authors.lastname: Pavlica
authors.forename: Javorina
authors.initials: J
authors.lastname: Milosevic
authors.forename: Mario
authors.initials: M
authors.lastname: Keller
authors.forename: Mattes
authors.initials: M
authors.lastname: Schulze
authors.forename: Frank
authors.initials: F
authors.lastname: Peinemann
authors.forename: Antonella
authors.initials: A
authors.lastname: Piscioneri
authors.forename: Loredana
authors.initials: L
authors.lastname: De Bartolo
authors.forename: Kai
authors.initials: K
authors.lastname: Darsow
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bartel
authors.forename: Harald A
authors.initials: HA
authors.lastname: Lange
authors.forename: Augustinus
authors.initials: A
authors.lastname: Bader
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004921:Erythropoietin / Q000494:pharmacology*; D053686:Fetal Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D017467:Receptors, Erythropoietin / Q000378:metabolism
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin