Expression analysis of neuroglobin mRNA in rodent tissues

Reuss, Stefan; Saaler-Reinhardt, Sigrid; Weich, Bettina; Wystub, Sylvia; Reuss, Martina H.; Burmester, Thorsten; Hankeln, Thomas

doi:10.1016/s0306-4522(02)00536-5

Cited by 164 publications

(172 citation statements)

References 26 publications

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“…RT-PCR of tissue from several brain regions showed that wild-type controls expressed Ngb diffusely throughout the brain (Figure 2A), consistent with previous reports (Burmester et al, 2000;Reuss et al, 2002). F1 founders showed increased Ngb signal, as well as GFP signal consistent with the transgenic origin of this increase.…”

Section: Production Of Trangenic Mousesupporting

confidence: 90%

A neuroglobin-overexpressing transgenic mouse

Khan¹,

Sun²,

Jin³

et al. 2007

Gene

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Neuroglobin (Ngb) is a recently discovered vertebrate globin expressed primarily in neurons. Ngb expression is induced by hypoxia and ischemia, and Ngb protects neurons from these insults. However, its normal physiological role and the mechanism underlying its neuroprotective action are uncertain. We report production of a transgenic mouse in which Ngb is overexpressed under the control of the chicken β-actin promoter. This mouse should prove helpful for studying Ngb-mediated effects in vitro and in vivo.

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Section: Production Of Trangenic Mousesupporting

confidence: 90%

A neuroglobin-overexpressing transgenic mouse

Khan¹,

Sun²,

Jin³

et al. 2007

Gene

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“…These results mainly confirm previous in situ hybridization data (27,28). However, in contrast to Reuss et al (28) who claimed a more uniform distribution of mNgb throughout the distinct brain regions, we found a more focal distribution pattern of mNgb.…”

Section: A Globin In the Nucleus 30418supporting

confidence: 90%

A Globin in the Nucleus!

Geuens

Brouns

Flamez

et al. 2003

Journal of Biological Chemistry

147

134

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Cytoglobin and neuroglobin are recently discovered members of the globin family. In situ hybridization localized neuroglobin mainly in brain and retina, while cytoglobin was expressed ubiquitously in all analyzed tissues. In the present study, polyclonal antibodies were raised against both proteins and the distribution of them was studied by immunocytochemistry at tissue and subcellular level. Cytoglobin immunoreactivity was uniformly distributed and found in all tissues studied. At the subcellular level, cytoglobin immunoreactivity was exclusively detected in the cell nucleus. In contrast, neuroglobin immunoreactivity was detected in specific brain regions with varying intensities and in the islet of Langerhans in the pancreas. The immunoreactivity was restricted to the cytoplasm of neurons and endocrine beta cells. The nuclear localization of cytoglobin opens new perspectives for possible function(s) of globinfolded proteins as transcriptional regulators.The widespread occurrence of hemoglobins (Hbs) 1 in virtually all kingdoms indicates that the gene for Hb is very ancient and that Hbs may serve functions other than simple O 2 carriers (1-4). The actual function of the proteins of this superfamily is mainly associated with O 2 transport/storage. However, the reported involvement of bacterial (5), invertebrate (6) and vertebrate Hbs/myoglobins (Mbs) (7,8) in the detoxification of NO, might illustrate a more primitive function of these molecules (3). Involvement in other functions as O 2 scavenger (4), O 2 sensor (9), O 2 consuming enzymes (10), or shadow pigments (11) have been suggested and may illustrate the coincidental use of a stable protein fold during evolution.Recently, two new members of the vertebrate globin family, namely neuroglobin (Ngb) and cytoglobin (Cygb), have been discovered (12)(13)(14)(15)(16). Both are monomeric (151 and 190 amino acid residues, respectively), intracellular proteins, displaying all determinants of the globin fold. Sequence analyses reveal low sequence identity with vertebrate Hb and Mb (20 -25%), as well as a very ancient origin, i.e. much older than Mb (16). The heme-iron atom of Ngb and Cygb is hexacoordinated, showing a His-Fe-His binding scheme, both histidines being the proximal and the distal histidine, respectively (13,15,17). Ngb has a high recombination rate (k on ) and a slow dissociation rate (k off ), indicating a high intrinsic affinity for the ligands (O 2 / CO). Before binding, the external ligands must compete with the internal sixth ligand, resulting in an observed O 2 affinity of the recombinant proteins similar to that of Mb (1 torr at 37°C).The function of Ngb and Cygb is a matter of debate. In response to hypoxia, Ngb is up-regulated in vivo and in vitro and protects the neurons against hypoxic damage (18). High concentrations (ϳ100 M) of Ngb are observed in the retina and its subcellular distribution correlates with the localization of the mitochondria (19). Both observations suggest a role in intracellular O 2 supply.A protein, identical to Cygb a...

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“…The recent discovery of neuroglobin (Ngb; ref. 14), which is expressed primarily in cerebral neurons (15), is induced by neuronal hypoxia and cerebral ischemia (16) and protects neurons from hypoxia in vitro (16), suggests that this protein may have a role in sensing or responding to neuronal hypoxia, which could have implications for the pathophysiology and treatment of stroke.…”

mentioning

confidence: 99%

Neuroglobin protects the brain from experimental stroke in vivo

Sun

Jin²,

Peel

et al. 2003

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

340

344

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Neuroglobin (Ngb) is an O2-binding protein localized to cerebral neurons of vertebrates, including humans. Its physiological role is unknown but, like hemoglobin, myoglobin, and cytoglobin͞histo-globin, it may transport O 2, detoxify reactive oxygen species, or serve as a hypoxia sensor. We reported recently that hypoxia stimulates transcriptional activation of Ngb in cultured cortical neurons and that antisense inhibition of Ngb expression increases hypoxic neuronal injury, whereas overexpression of Ngb confers resistance to hypoxia. These findings are consistent with a role for Ngb in promoting neuronal survival after hypoxic insults in vitro. Here we report that in rats, intracerebroventricular administration of an Ngb antisense, but not sense, oligodeoxynucleotide increases infarct volume and worsens functional neurological outcome, whereas intracerebral administration of a Ngb-expressing adenoassociated virus vector reduces infarct size and improves functional outcome, after focal cerebral ischemia induced by occlusion of the middle cerebral artery. We conclude that Ngb acts as an endogenous neuroprotective factor in focal cerebral ischemia and may therefore represent a target for the development of new treatments for stroke.T he ability to sense and respond to hypoxia is a universal attribute of eukaryotic cells, but the role of this ability in protecting cells from ischemic insults and its potential for therapeutic application are unclear. One prominent feature of cellular adaptation to hypoxia or ischemia consists of the increased expression of hypoxia-inducible proteins (1), including proteins with the capacity to protect the brain from ischemic insults (2, 3). Examples include hypoxia-inducible factor-1 (4), erythropoietin (5), vascular endothelial growth factor (6), heme oxygenase-1 (7), and adrenomedullin (8). These proteins are likely to exert their neuroprotective effects through diverse mechanisms but their hypoxia-responsiveness depends ultimately on O 2 -binding proteins that can sense hypoxia and trigger appropriate cellular adaptations (9, 10).The globins are a family of heme proteins that can bind, transport, scavenge, detoxify, and sense gases like O 2 and NO (11). Four vertebrate globins have been identified. Hemoglobin, which differs from other vertebrate globins in occurring as a tetramer, is localized to erythrocytes and transports O 2 between the lungs and other tissues. Myoglobin (Mgb) is monomeric and is localized to the cytoplasm of skeletal and cardiac myocytes. Cytoglobin or histoglobin (12, 13) is expressed widely in both neural and nonneural vertebrate tissues, but its functions are unknown. The recent discovery of neuroglobin (Ngb; ref. 14), which is expressed primarily in cerebral neurons (15), is induced by neuronal hypoxia and cerebral ischemia (16) and protects neurons from hypoxia in vitro (16), suggests that this protein may have a role in sensing or responding to neuronal hypoxia, which could have implications for the pathophysiology and treatment of stroke.To test the hy...

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Expression analysis of neuroglobin mRNA in rodent tissues

Cited by 164 publications

References 26 publications

A neuroglobin-overexpressing transgenic mouse

A neuroglobin-overexpressing transgenic mouse

A Globin in the Nucleus!

Neuroglobin protects the brain from experimental stroke in vivo

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