title: Erythropoietin modulates autophagy signaling in the developing rat brain in an in vivo model of oxygen-toxicity.
abstract: Autophagy is a self-degradative process that involves turnover and recycling of cytoplasmic components in healthy and diseased tissue. Autophagy has been shown to be protective at the early stages of programmed cell death but it can also promote apoptosis under certain conditions. Earlier we demonstrated that oxygen contributes to the pathogenesis of neonatal brain damage, which can be ameliorated by intervention with recombinant human erythropoietin (rhEpo). Extrinsic- and intrinsic apoptotic pathways are involved in oxygen induced neurotoxicity but the role of autophagy in this model is unclear. We analyzed the expression of autophagy activity markers in the immature rodent brain after exposure to elevated oxygen concentrations. We observed a hyperoxia-exposure dependent regulation of autophagy-related gene (Atg) proteins Atg3, 5, 12, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), LC3A-II, and LC3B-II which are all key autophagy activity proteins. Interestingly, a single injection with rhEpo at the onset of hyperoxia counteracted these oxygen-mediated effects. Our results indicate that rhEpo generates its protective effect by modifying the key autophagy activity proteins.
authors.affiliation: Department of Pediatrics I, Neonatology, University Hospital Essen, 45122 Essen, Germany. ivo.bendix@uk-essen.de.
authors.forename: Ivo
authors.initials: I
authors.lastname: Bendix
authors.forename: Corina
authors.initials: C
authors.lastname: Schulze
authors.forename: Clarissa von
authors.initials: Cv
authors.lastname: Haefen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gellhaus
authors.forename: Stefanie
authors.initials: S
authors.lastname: Endesfelder
authors.forename: Rolf
authors.initials: R
authors.lastname: Heumann
authors.forename: Ursula
authors.initials: U
authors.lastname: Felderhoff-Mueser
authors.forename: Marco
authors.initials: M
authors.lastname: Sifringer
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D023421:Models, Animal; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D000068817:Epoetin Alfa; D004921:Erythropoietin; D008869:Microtubule-Associated Proteins; D010453:Peptide Synthases; D011506:Proteins; D011994:Recombinant Proteins; C545865:Atg5 protein, rat; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C515644:Atg3 protein, rat