17β-estradiol--a new modulator of neuroglobin levels in neurons: role in neuroprotection against H₂O₂-induced toxicity

Neurosignals. 2010;18(4):223-35. doi: 10.1159/000323906. Epub 2011 Feb 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytoprotection / drug effects
  • Cytoprotection / physiology
  • Estradiol / pharmacology
  • Estradiol / physiology*
  • Globins / drug effects
  • Globins / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Hydrogen Peroxide / antagonists & inhibitors*
  • Hydrogen Peroxide / toxicity
  • Mice
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / metabolism*
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neuroglobin
  • Neurons / drug effects*
  • Neurons / physiology
  • Neuroprotective Agents* / pharmacology
  • Oxidants / antagonists & inhibitors
  • Oxidants / toxicity

Substances

  • Nerve Tissue Proteins
  • Neuroglobin
  • Neuroprotective Agents
  • Oxidants
  • Estradiol
  • Globins
  • Hydrogen Peroxide