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Xin Xin Xiong, Feng Pan, Ruo Qiao Chen, Dian Xing Hu, Xin Yao Qiu, Chun Yang Li, Xiao Qiang Xie, Bo Tian, Xiao Qian Chen
Cerebral ischemia causes severe cell death or injury including axon breakdown or retraction in the brain. Axon regeneration is crucial for the functional recovery of injured neurons or brains after ischemia/reperfusion (I/R); however, this process has been proved extremely difficult in adult brains and there is still no effective therapy for it. Here we reported that neuroglobin (Ngb), a novel oxygen-binding or sensor protein existing predominantly in neurons or brains, functions as a driving factor for axon regeneration during I/R...
February 7, 2018: Cell Death & Disease
Tina Garofalo, Alberto Ferri, Maurizio Sorice, Pardis Azmoon, Maria Grasso, Vincenzo Mattei, Antonella Capozzi, Valeria Manganelli, Roberta Misasi
Since stressing conditions induce a relocalization of endogenous human neuroglobin (NGB) to mitochondria, this research is aimed to evaluate the protective role of NGB overexpression against neurotoxic stimuli, through mitochondrial lipid raft-associated complexes. To this purpose, we built a neuronal model of oxidative stress by the use of human dopaminergic neuroblastoma cells, SK-N-BE2, stably overexpressing NGB by transfection and treated with 1-methyl-4-phenylpyridinium ion (MPP+). We preliminary observed the redistribution of NGB to mitochondria following MPP+ treatment...
January 26, 2018: Molecular and Cellular Neurosciences
Evi Luyckx, Wendy Van Leuven, Daniel Andre, Alessandra Quarta, Kristien Reekmans, Erik Fransen, Luc Moens, Thomas Hankeln, Peter Ponsaerts, Sylvia Dewilde
In the quest to unravel its functional significance, neuroglobin (Ngb), a brain-specific neuroprotective protein, has recently been proposed as an actor in neurodevelopment. As neural stem cells (NSCs) are fundamental during brain development, the present study aimed at investigating the role of Ngb in the growth and proliferation of NSCs by comparing an Ngb-floxed (Ngbfl -)NSC line, equivalent to the wild-type cellular situation, with an in-house created Ngb knockout (NgbKO -)NSC line. NgbKO -NSCs were characterized by an increased growth and proliferation capacity in vitro, supported by RNA sequencing and western blot results reporting the downregulation of Cdkn1a and the upregulation of Cdk6, both enhancing the cell cycle...
February 27, 2018: Stem Cells and Development
Marco Fiocchetti, Manuela Cipolletti, Paolo Ascenzi, Maria Marino
Neuroglobin (NGB) is a relatively recent discovered monomeric heme-protein, which behave in neurons as a sensor of injuring stimuli including oxidative stress, hypoxia, and neurotoxicity. In addition, the anti-apoptotic activity of overexpressed NGB has been reported both in neurons and in cancer cell lines. We recently demonstrated that, NGB functions as a compensatory protein of the steroid hormone 17β-estradiol (E2) protecting cancer cells against the apoptotic death induced by oxidative stress. However, the E2-induced signaling pathways at the root of NGB over-expression and mitochondrial re-localization in breast cancer cells is still elusive...
December 8, 2017: Journal of Cellular Physiology
Marco Fiocchetti, Manuela Cipolletti, Maria Marino
Environmental factors or adverse growth conditions that may reduce cell function or viability are considered stress. The cell ability to sense and respond to environmental stresses determine its function and survival destiny. We recently defined Neuroglobin (NGB), a heme-protein, as a compensatory protein in the 17β-Estradiol (E2) anti-apoptotic activity and as a sensor of oxidative stress in both neurons and breast cancer cells. Here, the possibility that NGB levels could represent a pivotal regulator of integrated response of cancer cells to stress has been evaluated...
2017: PloS One
Bei Zhang, Yong Liu, Yajun Li, Xiao Zhe, Shijun Zhang, Lei Zhang
Our previous study demonstrated that neuroglobin (Ngb) functions as an independent predictive indicator of the prognosis of patients with glioma and promotes cancer cell growth by suppressing apoptosis. However, the understanding of the mechanisms underlying the survival‑enhancing function of Ngb in glioma is limited. In the present study, KEGG PathwayFinder by gene correlation analysis was performed on the R2: Genomics Analysis and Visualization Platform, which revealed a high association between Ngb and the phosphatidylinositol 3‑kinase (PI3K)/AKT pathway using glioma data (GSE4290) from the Gene Expression Omnibus database...
February 2018: Molecular Medicine Reports
An Bracke, David Hoogewijs, Sylvia Dewilde
Globins are among the best investigated proteins in biological and medical sciences and represent a prime tool for the study of the evolution of genes and the structure-function relationship of proteins. Here, we explore the recombinant expression of globins in three different expression systems: Escherichia coli, Pichia pastoris and the baculovirus infected Spodoptera frugiperda. We expressed two different human globin types in these three expression systems: I) the well-characterized neuroglobin and II) the uncharacterized, circular permutated globin domain of the large chimeric globin androglobin...
February 15, 2018: Analytical Biochemistry
Jianping Niu, Rui Hu
This study aimed to explore the role and mechanism(s) of flunarizine hydrochloride in the intracerebral hemorrhage (ICH) rats. The 32 adult male Sprague Dawley (SD) rats were randomly assigned into four groups: control group, sham group, ICH group, and FLU + ICH group. The effects of flunarizine hydrochloride were assessed on the basis of hematoma volume, blood-brain barrier (BBB) integrity, and brain water content in the ICH rat models. The role of flunarizine hydrochloride in cell recovery was assessed by behavioral scores, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assay...
November 1, 2017: International Journal of Immunopathology and Pharmacology
Ji-Lin Dai, Yun Lin, Yong-Jian Yuan, Shi-Tong Xing, Yi Xu, Qiang-Hua Zhang, Ji-Kang Min
OBJECTIVE: The present study was aimed to investigate the therapeutic potential of neuroglobin in the recovery of spinal cord injury. METHODS: The male albino Wistar strain rats were used as an experimental model, and adeno associated virus (AAV) was administered in the T12 section of spinal cord ten days prior to the injury. Basso Beattie Bresnahan (BBB) locomotor rating scale was used to determine the recovery of the hind limb during four weeks post-operation...
November 16, 2017: Journal of Spinal Cord Medicine
Nathalie Colloc'h, Philippe Carpentier, Laura C Montemiglio, Beatrice Vallone, Thierry Prangé
Internal cavities are crucial for conformational flexibility of proteins and can be mapped through noble gas diffusion and docking. Here we investigate the hydrophobic cavities and tunnel network in neuroglobin (Ngb), a hexacoordinated heme protein likely to be involved in neuroprotection, using crystallography under noble gas pressure, mostly at room temperature. In murine Ngb, a large internal cavity is involved in the heme sliding mechanism to achieve binding of gaseous ligands through coordination to the heme iron...
November 21, 2017: Biophysical Journal
A Cardinale, F R Fusco, E Paldino, C Giampà, M Marino, M T Nuzzo, V D'Angelo, D Laurenti, G Straccia, D Fasano, D Sarnataro, T Squillaro, S Paladino, Mariarosa A B Melone
Neuroglobin (Ngb) is expressed in the central and peripheral nervous system, cerebrospinal fluid, retina, and endocrine tissues where it is involved in binding O2 and other gasotransmitters. Several studies have highlighted its endogenous neuroprotective function. Huntington's disease (HD), a dominant hereditary disease, is characterized by the gradual loss of neurons in discrete areas of the central nervous system. We analyzed the expression of Ngb in the brain tissue of a mouse model of HD, in order to define the role of Ngb with respect to individual cell type vulnerability in HD and to gender and age of mice...
November 3, 2017: Neurological Sciences
Evi Luyckx, Bert R Everaert, Bieke Van der Veken, Wendy Van Leuven, Jean-Pierre Timmermans, Christiaan J Vrints, Guido R Y De Meyer, Wim Martinet, Sylvia Dewilde
Neuroglobin (NGB) is an oxygen-binding protein that is mainly expressed in nervous tissues where it is considered to be neuroprotective during ischemic brain injury. Interestingly, transgenic mice overexpressing NGB reveal cytoprotective effects on tissues lacking endogenous NGB, which might indicate a therapeutic role for NGB in a broad range of ischemic conditions. In the present study, we investigated the effect of NGB overexpression on survival as well as on the size and occurrence of myocardial infarctions (MI) in a mouse model of acute MI (AMI) and a model of advanced atherosclerosis (ApoE (-/-) Fbn1 (C1039G+/-) mice), in which coronary plaques and MI develop in mice being fed a Western-type diet...
November 2, 2017: Heart and Vessels
J Projecto-Garcia, A-S Le Port, T Govindji, D Jollivet, S W Schaeffer, S Hourdez
Hypoxia at deep-sea hydrothermal vents represents one of the most basic challenges for metazoans, which then requires specific adaptations to acquire oxygen to meet their metabolic needs. Hydrothermal vent scale-worms (Polychaeta; Polynoidae) express large amounts of extracellular single- and multi-domain hemoglobins, in contrast with their shallow-water relatives that only possess intracellular globins in their nervous system (neuroglobins). We sequenced the gene encoding the single-domain (SD) globin from nine species of polynoids found in various vent and deep-sea reduced microhabitats (and associated constraints) to determine if the Polynoidae SD globins have been the targets of diversifying selection...
December 2017: Journal of Molecular Evolution
Marzia Bellei, Carlo Augusto Bortolotti, Giulia Di Rocco, Marco Borsari, Lidia Lancellotti, Antonio Ranieri, Marco Sola, Gianantonio Battistuzzi
Neuroglobin is a monomeric globin containing a six-coordinate heme b, expressed in the nervous system, which exerts an important neuroprotective role. In the human protein (hNgb), Cys46 and Cys55 form an intramolecular disulfide bond under oxidizing conditions, whose cleavage induces a helix-to-strand rearrangement of the CD loop that strengthens the bond between the heme iron and the distal histidine. Hence, it is conceivable that the intramolecular disulfide bridge modulates the functionality of human neuroglobin by controlling exogenous ligand binding...
October 16, 2017: Journal of Inorganic Biochemistry
Ye Tao, Zhen Yang, Wei Fang, Zhao Ma, Yi Fei Huang, Zhengwei Li
Retinal degeneration (RD) is a heterogeneous group of inherited dystrophies leading to blindness. The N-methyl-N-nitrosourea (MNU)-administered mouse is used as a pharmacologically induced RD animal model in various therapeutic investigations. The present study found the retinal neuroglobin (NGB) expression in the MNU-administered mice was significantly lower than in normal controls, suggesting NGB was correlated with RD. Subsequently, an adeno-associated virus (AAV)-2-mCMV-NGB vector was delivered into the subretinal space of the MNU-administered mice...
2017: Therapeutics and Clinical Risk Management
Ye Tao, Zhao Ma, Bei Liu, Wei Fang, Limin Qin, Yi Fei Huang, Lu Wang, Yanling Gao
Retina is a critical component of the central nerve system that is responsible for the conversion of light stimulus into electrical spikes. Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited retinal dystrophies leading to blindness. We examined retinal neuroglobin (Ngb) expression in a pharmacologically induced RP animal model, the N-Methyl-N-nitrosourea (MNU) administered mice. The retinal Ngb expression in MNU administered mice attenuated following a time dependent manner, suggesting Ngb was involved in the photoreceptor degeneration...
January 1, 2018: Brain Research
Manuela Nowotny, Lenneke Kiefer, Daniel Andre, Andrej Fabrizius, Thomas Hankeln, Stefan Reuss
Neuroglobin (Ngb) is a member of the globin family of respiratory proteins, which was recently observed in many neurons of the auditory pathways. Up to now, however, nothing was known about the role of Ngb in hearing processes. We therefore studied auditory function by recording distortion-product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABRs) in wild-type (C57BL/6N) and Ngb-knockout mice. In KO mice, DPOAE thresholds were moderately augmented in the range of 5-18 kHz, reaching statistical significance at 8 and 10 kHz, while the ABR thresholds were not different between groups...
October 13, 2017: Neuroscience
Kayo Sugitani, Yoshiki Koriyama, Mayuko Sera, Kunizo Arai, Kazuhiro Ogai, Keisuke Wakasugi
Neuroglobin (Ngb) is a recently discovered heme protein in the vertebrate brain that can bind to oxygen molecules. Mammalian Ngb plays a crucial role in neuroprotection under conditions of oxidative stress. To investigate other potential functions of Ngb, we investigated the mouse retinal Ngb system following optic nerve injury. In the retina of control mice, Ngb immunoreactivity was limited to the retinal ganglion cell (RGC) layer, and this immunoreactivity rapidly decreased to less than 50% of the control level 5 days after optic nerve injury...
November 25, 2017: Biochemical and Biophysical Research Communications
Oscar Hidalgo-Lanussa, Marco Ávila-Rodriguez, Eliana Baez-Jurado, Jairo Zamudio, Valentina Echeverria, Luis Miguel Garcia-Segura, George E Barreto
High concentrations of palmitic acid in plasma increase both the inflammation associated with obesity and the susceptibility to develop a neurodegenerative event. In the brain, the inflammatory response is mediated by activated microglial cells, which undergo morphological and biochemical changes and can directly affect cell viability. Recent evidence shows that the use of estrogenic compounds can control microglia-induced inflammation with promising results. In this study, we explored the actions of the synthetic steroid tibolone on BV-2 microglia cells stimulated with palmitic acid...
September 25, 2017: Molecular Neurobiology
Rodrigo Rodrigues da Conceição, Janaina Sena de Souza, Kelen Carneiro de Oliveira, Rui Monteiro de Barros Maciel, Marco Aurélio Romano, Renata Marino Romano, Magnus Régios Dias da Silva, Maria Izabel Chiamolera, Gisele Giannocco
No abstract text is available yet for this article.
December 2017: Metabolic Brain Disease
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