17β-Estradiol - A New Modulator of Neuroglobin Levels in Neurons: Role in Neuroprotection against H2O2-Induced Toxicity

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 17 beta-estradiol (E-2) signaling in both SK-N-BE human neuroblastoma cell line and mouse hippocampal neurons. 1 nm E-2 rapidly induced a 300% increase in Ngb levels in both models. The E-2 effect was specific, being not induced by testosterone or dihydrotestosterone. The E-2-induced Ngb increase requires estrogen receptor (ER) 13, but not ERG, as evaluated by the mimetic effect of ER beta-specific agonist DPN and by the blockage of E-2 effect in ER beta-silenced SK-N-BE cells. Furthermore, both rapid (15 min) ER beta-dependent activation of p38/MAPK and transcriptional ER beta activity were required for the estrogenic regulation of Ngb. Finally, E-2 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 E-2 signaling mechanism that is activated to exert protective effects against H2O2-induced neurotoxicity. Copyright (C) 2011 S. Karger AG, Basel