title: Three weeks of erythropoietin treatment hampers skeletal muscle mitochondrial biogenesis in rats.
abstract: The blood O(2)-carrying capacity is maintained by the O(2)-regulated production of erythropoietin (Epo), which stimulates the proliferation and survival of red blood cell progenitors. Epo has been thought to act exclusively on erythroid progenitor cells. However, recent studies have identified the erythropoietin receptor (EpoR) in other cells, such as neurons, astrocytes, microglia, heart, cancer cell lines, and skeletal muscle provides evidence for a potential role of Epo in other tissues. In this study we aimed to determine the effect of recombinant human erythropoietin (rHuEpo) on skeletal muscle adaptations such as mitochondrial biogenesis, myogenesis, and angiogenesis in different muscle fibre types. Fourteen male Wistar rats were randomly divided into two experimental groups, and saline or rHuEpo (300 IU) was administered subcutaneously three times a week for 3 weeks. We evaluated the protein expression of intermediates involved in the mitochondrial biogenesis cascade, the myogenic cascade, and in angiogenesis in the oxidative soleus muscle and in the glycolytic gastrocnemius muscle. Contrary to our expectations, rHuEpo significantly hampered the mitochondrial biogenesis pathway in gastrocnemius muscle (PGC-1α, mTFA and cytochrome c). We did not find any effect of the treatment on cellular signals of myogenesis (MyoD and Myf5) or angiogenesis (VEGF) in either soleus or gastrocnemius muscles. Finally, we found no significant effect on the maximal aerobic velocity at the end of the experiment in the rHuEpo-treated animals. Our findings suggest that 3 weeks of rHuEpo treatment, which generates an increase of oxygen carrying capacity, can affect mitochondrial biogenesis in a muscle fibre-specific dependent manner.
authors.affiliation: Department of Physiology, University of Valencia, Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, Valencia, Spain.
authors.forename: Vladimir E
authors.initials: VE
authors.lastname: Martinez-Bello
authors.forename: Fabian
authors.initials: F
authors.lastname: Sanchis-Gomar
authors.forename: Marco
authors.initials: M
authors.lastname: Romagnoli
authors.forename: Frederic
authors.initials: F
authors.lastname: Derbre
authors.forename: Mari Carmen
authors.initials: MC
authors.lastname: Gomez-Cabrera
authors.forename: Jose
authors.initials: J
authors.lastname: Viña
mesh_terms: D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D004921:Erythropoietin / Q000008:administration & dosage*; D017079:Exercise Tolerance / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000502:physiology*; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051265:NF-E2-Related Factor 1 / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage; D012156:Reticulocytes / Q000166:cytology; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D051265:NF-E2-Related Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C489030:Tfam protein, rat; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004921:Erythropoietin; D045304:Cytochromes c