17β-Estradiol - A new modulator of neuroglobin levels in neurons: Role in neuroprotection against H 2O 2-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 17β-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) β, but not ERα, as evaluated by the mimetic effect of ERβ-specific agonist DPN and by the blockage of E 2 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, E 2 exerted a protective effect against H 2O 2-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 H 2O 2-induced neurotoxicity. Copyright © 2011 S. Karger AG, Basel.