Neuroglobin, estrogens, and neuroprotection

Abstract

SummaryGlobins have been found in glial cells and neurons of invertebrates and vertebrates. The first nerve globin has been recognized in the nerve cord of the polychaete annelid Aphrodite aculeata in 1872. In some invertebrates, the nerve globin reaches a millimolar concentration which is likely sufficient to sustain the aerobic metabolism and thus the excitability of the nervous system. In 2000, the first vertebrate nerve globin, named neuroglobin (Ngb), has been identified in neuronal tissues of mice and humans. In contrast to invertebrate nerve globins, the concentration of Ngb, the prototype of vertebrate nerve globins, is low (lM), reaching a maximum of 100 lM in retina cells. Therefore, Ngb appears unlikely to act primarily as an O 2 buffer and to facilitate O 2 diffusion to the mitochondria. Indeed, Ngb has been hypothesized to catalyze the formation/decomposition of reactive nitrogen and/or oxygen species and to be part of intracellular signaling pathways enhancing cell survival. Here, we report that neuronal Ngb levels are strongly induced by the steroid hormone 17b-estradiol. Furthermore, Ngb participates to mechanisms involved in 17b-estradiol-induced protective effects against H 2 O 2 -induced neurotoxicity.

Neuroglobin upregulation induced by 17β-estradiol sequesters cytocrome c in the mitochondria preventing H2O2-induced apoptosis of neuroblastoma cells

“…In this scenario, the E2 function is to accelerate the protective cell response to external insults 21 by inducing a rapid and strong increase and reallocation of endogenous NGB, which in turn is pivotal to impair the activation of the intrinsic apoptotic pathway by direct interaction with cytochrome c in the mitochondria. However, further in vivo studies that will take into account the important role of E2 in NGB induction are required to better understand how this new mechanism of NGB endogenous modulation can be utilized to enhance the brain protective mechanisms.…”

“…The E2-induced NGB upregulation is pivotal for the neuroprotective effect of E2 against H 2 O 2 -induced toxicity. 20, 21 These results open the possibility that the protective role played by the E2-induced NGB could arise from NGB intervention in the mitochondrial apoptotic pathway and, in particular, from the association of NGB with cytochrome c in neuronal cells. Therefore, the aim of this work is to evaluate this hypothesis by assessing the interaction between NGB and cytochrome c in the presence of H 2 O 2 as pro-apoptotic factor and E2 as a survival agent in SK-N-BE neuroblastoma cell line.…”

Neuroprotective Effects of 17β-Estradiol Rely on Estrogen Receptor Membrane Initiated Signals

“…In fact, cell pre-treatment with the specific ERβ-inhibitor THC completely prevents E2 effects (De Marinis et al, 2010). Interestingly, the monomeric globin neuroglobin (Ngb), displaying a protective function in the brain (Fago et al, 2008; Burmester and Hankeln, 2009; Yu et al, 2009; De Marinis et al, 2010, 2011; DellaValle et al, 2010), is pivotal in ERβ-mediated effects on neuroprotection (De Marinis et al, 2010). The E2 effect on Ngb expression is rapid (1 h), persistent (24 h), specific, and mediated by the ERβ subtype.…”

“…As members of ligand-regulated transcription factor family, classically, ERs were thought to mediate only the E2 long-term transcriptional effects. However, a growing body of evidence highlighted rapid, membrane initiated E2 effects that are independent of the ER transcriptional control (Raz et al, 2008; Arnold and Beyer, 2009; De Marinis et al, 2011; Roepke et al, 2011). …”

Molecular adaptations in Antarctic fish and marine microorganisms

“…1A, B, C). However, the molecular mechanisms underlying the neuroprotective function of Ngb are still unclear, as extensively discussed by De Marinis et al (2011).…”