title: 17β-estradiol--a new modulator of neuroglobin levels in neurons: role in neuroprotection against H₂O₂-induced toxicity.
abstract: Although discovered in 2000, neuroglobin (Ngb) functions are still uncertain. A contribution to the role played by Ngb in neurons could certainly derive from the identification of Ngb endogenous modulators. Here, we evaluate the possibility that Ngb could be regulated by 17β-estradiol (E₂) signaling in both SK-N-BE human neuroblastoma cell line and mouse hippocampal neurons. 1 nM E₂ rapidly induced a 300% increase in Ngb levels in both models. The E₂ effect was specific, being not induced by testosterone or dihydrotestosterone. The E₂-induced Ngb increase requires estrogen receptor (ER) β, but not ERα, as evaluated by the mimetic effect of ERβ-specific agonist DPN and by the blockage of E₂ effect in ERβ-silenced SK-N-BE cells. Furthermore, both rapid (15 min) ERβ-dependent activation of p38/MAPK and transcriptional ERβ activity were required for the estrogenic regulation of Ngb. Finally, E₂ exerted a protective effect against H₂O₂-induced neuroblastoma cell death which was completely prevented in Ngb-silenced cells. Overall, these data suggest that Ngb is part of the E₂ signaling mechanism that is activated to exert protective effects against H₂O₂-induced neurotoxicity.
authors.affiliation: Department of Biology, University Roma Tre, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: De Marinis
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Marco
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Paola
authors.initials: P
authors.lastname: Galluzzo
authors.forename: Pamela
authors.initials: P
authors.lastname: Bulzomi
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Arevalo
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Maria
authors.initials: M
authors.lastname: Marino
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005914:Globins / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D000078787:Neuroglobin; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000633:toxicity
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D016877:Oxidants; D004958:Estradiol; D005914:Globins; D006861:Hydrogen Peroxide