E2 Regulates Epigenetic Signature on Neuroglobin Enhancer-Promoter in Neuronal Cells

Guglielmotto, Michela; Reineri, Stefania; Iannello, Andrea; Ferrero, Giulio; Vanzan, Ludovica; Miano, Valentina; Ricci, Luisa; Tamagno, Elena; Bortoli, Michele De; Cutrupi, Santina

doi:10.3389/fncel.2016.00147

Cited by 14 publications

(16 citation statements)

References 48 publications

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“…Administration of 17β-estradiol (E2) was also reported to upregulate Ngb levels in mouse hippocampal neurons and primary cortical astrocytes [ 221 , 222 ]. Interestingly, whereas no estrogen response element is found within the Ngb promoter, Guglielmotto and colleagues demonstrated that E2 induces the recruitment of estrogen receptor alpha (ERα) to the first intron of Ngb that acts as an enhancer element, which in turn induces chromatin remodeling and leads to enhanced Ngb expression [ 223 ]. In a model of brain-induced ischemia in gerbils, administration of recombinant human neuronal erythropoietin resulted in Ngb upregulation and reduced neuronal death [ 224 ].…”

Section: Neuroglobinmentioning

confidence: 99%

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

et al. 2020

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Vertebrate hemoglobin (Hb) and myoglobin (Mb) were among the first proteins whose structures and sequences were determined over 50 years ago. In the subsequent pregenomic period, numerous related proteins came to light in plants, invertebrates and bacteria, that shared the myoglobin fold, a signature sequence motif characteristic of a 3-on-3 α-helical sandwich. Concomitantly, eukaryote and bacterial globins with a truncated 2-on-2 α-helical fold were discovered. Genomic information over the last 20 years has dramatically expanded the list of known globins, demonstrating their existence in a limited number of archaeal genomes, a majority of bacterial genomes and an overwhelming majority of eukaryote genomes. In vertebrates, 6 additional globin types were identified, namely neuroglobin (Ngb), cytoglobin (Cygb), globin E (GbE), globin X (GbX), globin Y (GbY) and androglobin (Adgb). Furthermore, functions beyond the familiar oxygen transport and storage have been discovered within the vertebrate globin family, including NO metabolism, peroxidase activity, scavenging of free radicals, and signaling functions. The extension of the knowledge on globin functions suggests that the original roles of bacterial globins must have been enzymatic, involved in defense against NO toxicity, and perhaps also as sensors of O 2 , regulating taxis away or towards high O 2 concentrations. In this review, we aimed to discuss the evolution and remarkable functional diversity of vertebrate globins with particular focus on the variety of non-canonical expression sites of mammalian globins and their according impressive variability of atypical functions.

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Section: Neuroglobinmentioning

confidence: 99%

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

et al. 2020

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“…ERα regulates neuroglobin expression through genomic transcript region regulation (Guglielmotto et al, 2016 ). Estradiol is capable of upregulating neuroglobin through activation of ERß (De Marinis et al, 2013 ; Fiocchetti et al, 2015 ).…”

Section: Cytoarchitecture-specific Mechanism Involved In Sexual Diffementioning

confidence: 99%

Estradiol and the Development of the Cerebral Cortex: An Unexpected Role?

Denley¹,

Gatford²,

Sellers³

et al. 2018

Front. Neurosci.

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The cerebral cortex undergoes rapid folding in an “inside-outside” manner during embryonic development resulting in the establishment of six discrete cortical layers. This unique cytoarchitecture occurs via the coordinated processes of neurogenesis and cell migration. In addition, these processes are fine-tuned by a number of extracellular cues, which exert their effects by regulating intracellular signaling pathways. Interestingly, multiple brain regions have been shown to develop in a sexually dimorphic manner. In many cases, estrogens have been demonstrated to play an integral role in mediating these sexual dimorphisms in both males and females. Indeed, 17β-estradiol, the main biologically active estrogen, plays a critical organizational role during early brain development and has been shown to be pivotal in the sexually dimorphic development and regulation of the neural circuitry underlying sex-typical and socio-aggressive behaviors in males and females. However, whether and how estrogens, and 17β-estradiol in particular, regulate the development of the cerebral cortex is less well understood. In this review, we outline the evidence that estrogens are not only present but are engaged and regulate molecular machinery required for the fine-tuning of processes central to the cortex. We discuss how estrogens are thought to regulate the function of key molecular players and signaling pathways involved in corticogenesis, and where possible, highlight if these processes are sexually dimorphic. Collectively, we hope this review highlights the need to consider how estrogens may influence the development of brain regions directly involved in the sex-typical and socio-aggressive behaviors as well as development of sexually dimorphic regions such as the cerebral cortex.

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“…A previous study evaluated Ngb expression in astrocytes after brain trauma and reported that Ngb expression is present in subacute and chronic injuries but not acute trauma ( 28 ). Moreover, in other studies, it was found that Ngb is expressed in microglia and astrocytes specifically during conditions such as traumatic brain injury ( 84 , 122 ) and that estradiol regulates the expression of Ngb in astrocytes ( 66 ) through the estrogen receptor β (ERβ) ( 22 ), while ERα is involved in the regulation of Ngb in neurons ( 137 ). Interestingly, tibolone, a synthetic hormone with estrogenic, progestogenic, and androgenic actions, has also been reported to induce Ngb expression in astrocytic-like cells in vitro under glucose deprivation ( 65 ) (Figure 1 ).…”

Section: Neuroglobin Expression In Astrocytesmentioning

confidence: 99%

Protection by Neuroglobin Expression in Brain Pathologies

Báez¹,

Echeverrı́a²,

Cabezas³

et al. 2016

Front. Neurol.

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Astrocytes play an important role in physiological, metabolic, and structural functions, and when impaired, they can be involved in various pathologies including Alzheimer, focal ischemic stroke, and traumatic brain injury. These disorders involve an imbalance in the blood flow and nutrients such as glucose and lactate, leading to biochemical and molecular changes that cause neuronal damage, which is followed by loss of cognitive and motor functions. Previous studies have shown that astrocytes are more resilient than neurons during brain insults as a consequence of their more effective antioxidant systems, transporters, and enzymes, which made them less susceptible to excitotoxicity. In addition, astrocytes synthesize and release different protective molecules for neurons, including neuroglobin, a member of the globin family of proteins. After brain injury, neuroglobin expression is induced in astrocytes. Since neuroglobin promotes neuronal survival, its increased expression in astrocytes after brain injury may represent an endogenous neuroprotective mechanism. Here, we review the role of neuroglobin in the central nervous system, its relationship with different pathologies, and the role of different factors that regulate its expression in astrocytes.

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E2 Regulates Epigenetic Signature on Neuroglobin Enhancer-Promoter in Neuronal Cells

Cited by 14 publications

References 48 publications

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

Estradiol and the Development of the Cerebral Cortex: An Unexpected Role?

Protection by Neuroglobin Expression in Brain Pathologies

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