Localization of neuroglobin protein in the mouse brain

Wystub, Sylvia; Laufs, Tilmann; Schmidt, Marc; Burmester, Thorsten; Maas, Ulrike; Saaler-Reinhardt, Sigrid; Hankeln, Thomas; Reuss, Stefan

doi:10.1016/s0304-3940(03)00563-9

Cited by 107 publications

(86 citation statements)

References 9 publications

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“…1C). The Ngb signals in Spalax neurons were basically identical in regional distribution and intensity to those obtained from mice (19,39). Immunofluorescence detection of Ngb did not differ between brains prepared from normoxic and hypoxic (5 h, 6% O 2 ) Spalax.…”

Section: Resultssupporting

confidence: 62%

“…This quantitative difference can be interpreted in terms of an O 2 supply function and/or an ROS detoxification role of Ngb as an adaptive strategy to alleviate hypoxic stress. In Spalax, the interpretation is more complicated: we show that Ngb in the mole rat is localized in neurons and astrocytes, whereas in the brain of hypoxia-sensitive rodents like mouse or rat, Ngb is localized primarily in neurons (19,39,45). Thus, both cell types contribute to the elevated Ngb expression level in Spalax brain, and we are currently unable to separately quantify neuronal and glial expression.…”

Section: Increased Globin Levels In Spalax Indicate a Function In Hypmentioning

confidence: 90%

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Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat Spalax

Avivi

Gerlach²,

Joel³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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122

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The subterranean mole rat Spalax is an excellent model for studying adaptation of a mammal toward chronic environmental hypoxia. Neuroglobin (Ngb) and cytoglobin (Cygb) are O 2 -binding respiratory proteins and thus candidates for being involved in molecular hypoxia adaptations of Spalax. Ngb is expressed primarily in vertebrate nerves, whereas Cygb is found in extracellular matrix-producing cells and in some neurons. The physiological functions of both proteins are not fully understood but discussed with regard to O 2 supply, the detoxification of reactive oxygen or nitrogen species, and apoptosis protection. Spalax Ngb and Cygb coding sequences are strongly conserved. However, mRNA and protein levels of Ngb in Spalax brain are 3-fold higher than in Rattus norvegicus under normoxia. Importantly, Spalax expresses Ngb in neurons and additionally in glia, whereas in hypoxia-sensitive rodents Ngb expression is limited to neurons. Hypoxia causes an approximately 2-fold downregulation of Ngb mRNA in brain of rat and mole rat. A parallel regulatory response was found for myoglobin (Mb) in Spalax and rat muscle, suggesting similar functions of Mb and Ngb. Cygb also revealed an augmented normoxic expression in Spalax vs. rat brain, but not in heart or liver, indicating distinct tissue-specific functions. Hypoxia induced Cygb transcription in heart and liver of both mammals, with the most prominent mRNA up-regulation (12-fold) in Spalax heart. Our data suggest that tissue globins contribute to the remarkable tolerance of Spalax toward environmental hypoxia. This is consistent with the proposed cytoprotective effect of Ngb and Cygb under pathological hypoxic/ischemic conditions in mammals.

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Section: Resultssupporting

confidence: 62%

Section: Increased Globin Levels In Spalax Indicate a Function In Hypmentioning

confidence: 90%

Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat Spalax

Avivi

Gerlach²,

Joel³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

122

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“…Neuronal Expression of Ngb in the Vertebrate Brain-As in the central nervous system of mammals (6,19,21), Ngb was expressed in brain neurons (Figs. 3-6).…”

Section: Discussionmentioning

confidence: 99%

Zebrafish Reveals Different and Conserved Features of Vertebrate Neuroglobin Gene Structure, Expression Pattern, and Ligand Binding

Fuchs

Heib

Kiger

et al. 2004

Journal of Biological Chemistry

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Neuroglobin has been identified as a respiratory protein that is primarily expressed in the mammalian nervous system. Here we present the first detailed analysis of neuroglobin from a non-mammalian vertebrate, the zebrafish Danio rerio. The zebrafish neuroglobin gene reveals a mammalian-type exon-intron pattern in the coding region (B12.2, E11.0, and G7.0), plus an additional 5-non-coding exon. Similar to the mammalian neuroglobin, the zebrafish protein displays a hexacoordinate deoxy-binding scheme. Flash photolysis kinetics show the competitive binding on the millisecond timescale of external ligands and the distal histidine, resulting in an oxygen affinity of 1 torr. Western blotting, immune staining, and mRNA in situ hybridization demonstrate neuroglobin expression in the fish central nervous system and the retina but also in the gills. Neurons containing neuroglobin have a widespread distribution in the brain but are also present in the olfactory system. In the fish retina, neuroglobin is mainly present in the inner segments of the photoreceptor cells. In the gills, the chloride cells were identified to express neuroglobin. Neuroglobin appears to be associated with mitochondria-rich cell types and thus oxygen consumption rates, suggesting a myoglobin-like function of this protein in facilitated oxygen diffusion.Transport and storage of oxygen in vertebrate animals are typically mediated by globins, small proteins that bind O 2 by the means of a porphyrin-coordinated Fe 2ϩ ion (1-3). The heterotetrameric hemoglobin is present in red blood cells of nearly all vertebrates and transports O 2 in the circulatory system from the respiratory surfaces to the inner organs. The monomeric myoglobin, typically found in the myocytes of cardiac and striated muscles, facilitates intracellular O 2 diffusion to the mitochondria and stores O 2 (3, 4) but also functions as an nitric-oxide dioxygenase (5). Neuroglobin (Ngb) 1 and cytoglobin are two recently discovered vertebrate globins (6 -9). Whereas cytoglobin might play a role in collagen synthesis (10, 11), the leading hypotheses suggest Ngb to be involved in neuronal oxygen homeostasis (6,(12)(13)(14)(15)(16). Ngb shares only a few amino acids with vertebrate hemoglobin and myoglobin (Ͻ25% identity) but rather resembles the nerve-specific globins known in some invertebrates (6, 13). In fact, phylogenetic analyses suggest an ancient origin of Ngb, probably diverging from the other globins before the Protostomia-Deuterostomia split (6, 8). Mouse and human deoxy-Ngb display hexacordinated hemochrome-binding schemes at the Fe 2ϩ (17, 18). The proximal histidine can be replaced by an external ligand such as O 2 , resulting in an oxygen affinity (P 50 ) of ϳ1-2 torr, similar to that of myoglobin (6, 17).Initially, Ngb was found to be predominantly expressed in the brains of man and mouse (6), but recent analyses show Ngb to be also present in the peripheral nervous system and some non-neuronal endocrine tissues (19 -21). Particularly high amounts of Ngb were observed in the m...

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“…Ngb is widely and heterotopically expressed in the CNS, and is more particularly abundant in cerebral cortex, hippocampus, thalamus, hypothalamus, and cerebellum of rat brain (Geuens et al, 2003;Reuss et al, 2002;Wystub et al, 2003). Ngb appears to play a role in neuronal protection following hypoxic and ischemic insults (Khan et al, 2006;Sun et al, 2001;Sun et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Neuroglobin protects PC12 cells against oxidative stress

Morris

Lee

et al. 2008

Brain Research

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Neuroglobin (Ngb) is a newly discovered globin in the vertebrate brain that exhibits neuroprotection against hypoxic/ischemic injury. Hypoxic/ischemic brain injury is associated with accumulation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS), and antioxidants or ROS scavengers promote cell survival. Therefore, Ngb may serve as a scavenger of toxic reactive species, such as hydrogen peroxide. To examine the anti-oxidative role of neuroglobin, PC12 cells were transfected with wild-type and mutant (H64V/H96A) Ngb for 48 hours and then treated with H 2 O 2 (0.1, 0.2 and 0.4 mM) for 6 hours. Ngb siRNA decreased the H 2 O 2 induced Ngb expression and exacerbated H 2 O 2 induced cell injury. Transient transfection of Ngb induced dose-dependent increases in Ngb protein expression and did not alter SOD, GPX, and catalase activities. Overexpression of wild type Ngb, but not of mutant Ngb, significantly attenuated H 2 O 2 -induced ROS/RNS accumulation and lipid peroxidation, decreased H 2 O 2 induced mitochondrial dysfunction and apoptosis, and promoted overall cell survival. Thus, Ngb plays a protective role against oxidative stress, which appears to be primarily mediated by intrinsic Ngb antioxidant properties.

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Localization of neuroglobin protein in the mouse brain

Cited by 107 publications

References 9 publications

Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat Spalax

Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat Spalax

Zebrafish Reveals Different and Conserved Features of Vertebrate Neuroglobin Gene Structure, Expression Pattern, and Ligand Binding

Neuroglobin protects PC12 cells against oxidative stress

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