Hypoxia/Ischemia and the Regulation of Neuroglobin and Cytoglobin Expression

Fordel, Elke; Geuens, Eva; Dewilde, Sylvia; Coen, Wim De; Moëns, Luc

doi:10.1080/15216540500037406

Cited by 72 publications

(62 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the absolute levels of expression of CYGB were very low in three of the cell lines, which had promoter methylation 40.95. These data imply that there may be alternate control mechanisms for the activation of this gene and may be explained by observations of hypoxia responsive mRNA stabilisation sites in the gene (Fordel et al, 2004a). These trends largely replicate in vitro our ex vivo cross-sectional tissue data and lend further support to the role of tissue hypoxia in the regulation of CYGB.…”

Section: Discussionsupporting

confidence: 77%

“…Subsequent studies on hippocampal cell lines confirmed that hypoxia upregulates CYGB mRNA expression in a 'dose-dependent' manner (Fordel et al, 2004a, b). Further work on HIF1A ( þ /1) knockout mice confirmed that this effect is mediated by the HIF1A pathway and also that the CYGB gene contains hypoxia responsive elements and mRNA stabilisation sites (Fordel et al, 2004a). Hypoxia is a known endogenous marker of poor prognosis in HNSCC.…”

mentioning

confidence: 85%

“…Should Cygb prove to be a critical component in the hypoxia response, its manipulation might have therapeutic value, particularly in response to radiation treatment. Is the overexpression of CYGB necessary to mediate the hypoxia response, to mediate VEGF expression (Fordel et al, 2004a), to subtend a survival advantage in more aggressive tumours? Clearly more studies are necessary to clarify exactly where CYGB fits in to the cellular hypoxia story and whether it is up-or downstream of HIF1A, currently viewed as the orchestrator of the tumour's response to hypoxia.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: Cytoglobin (Cygb) was first described in 2002 as an intracellular globin of unknown function. We have previously shown the downregulation of cytoglobin as a key event in a familial cancer syndrome of the upper aerodigestive tract. METHOD: Cytoglobin expression and promoter methylation were investigated in sporadic head and neck squamous cell carcinoma (HNSCC) using a cross-section of clinical samples. Additionally, the putative mechanisms of Cygb expression in cancer were explored by subjecting HNSCC cell lines to hypoxic culture conditions and 5-aza-2-deoxycitidine treatment. RESULTS: In clinically derived HNSCC samples, CYGB mRNA expression showed a striking correlation with tumour hypoxia (measured by HIF1A mRNA expression P ¼ 0.013) and consistent associations with histopathological measures of tumour aggression. CYGB expression also showed a marked negative correlation with promoter methylation (P ¼ 0.018). In the HNSCC cell lines cultured under hypoxic conditions, a trend of increasing expression of both CYGB and HIF1A with progressive hypoxia was observed. Treatment with 5-aza-2-deoxycitidine dramatically increased CYGB expression in those cell lines with greater baseline promoter methylation. CONCLUSION: We conclude that the CYGB gene is regulated by both promoter methylation and tumour hypoxia in HNSCC and that increased expression of this gene correlates with clincopathological measures of a tumour's biological aggression.

show abstract

Section: Discussionsupporting

confidence: 77%

mentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Overexpression of NGB did not affect the basal level of IOP, and injection of microbeads in Ngb-Tg mice induced a kinetic of IOP elevation similar to that of the wild-type littermates ( Figure 1D). However, elevated IOP resulted in an increase in NGB expression in the retina, including the GCL, INL, and OPL, in wild-type mice ( Figure 1B), Neuroglobin 6 relative to expression in PBS-injected eyes. Immunolabeling of NGB in Ngb-Tg mice also confirmed high levels of NGB expression in the GCL and other retinal layers ( Figure 1C).…”

Section: Ngb Expression Profile In Response To Iop Elevationmentioning

confidence: 99%

Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

Wei

Cho

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Neuroglobin (NGB), a newly discovered member of the globin superfamily, may regulate neuronal survival under hypoxia or oxidative stress. Although NGB is greatly expressed in retinal neurons, the biological functions of NGB in retinal diseases remain largely unknown. We investigated the role of NGB in an experimental model of glaucoma, a neurodegenerative disorder that usually involves elevation of intraocular pressure (IOP). Elevated IOP is thought to induce oxidative stress in retinal ganglion cells (RGCs), thereby causing RGC death and, eventually, blindness. We found that NGB plays a critical role in increasing RGC resistance to ocular hypertension and glaucomatous damage. Neuroglobin (NGB) is a novel member of the globin superfamily that is distantly related to hemoglobin and myoglobin. 1 A highly conserved protein in evolution, human and mouse Ngb, both comprised of 151 amino acids, are 94% identical. 2,3 In mammals, expression of NGB is found in the brain, retina, and other nerve tissues, predominantly in neurons but absent from glial cells. 4 -7 Distribution of NGB protein in the normal human retina is very similar to what has been described in mice: NGB is detected primarily in the plexiform layers and photoreceptor inner segments, which are rich in mitochondria and synapses and consume high amounts of oxygen. 8,9 NGB has been shown to act as an endogenous neuroprotective molecule that enhances neuronal survival under hypoxic-ischemic insults in the brain 10 -12 ; however, its physiological functions and molecular mode of actions are not fully understood. Of note, NGB is present at a 100-fold greater concentration in the retina than in the brain, 8,[13][14][15] suggesting that the retina may be its most important site of function; however, among the many unknown roles of NGB, functional significance of NGB expression in the retina has been largely unexplored.

show abstract

“…Robust in vivo induction of Mb genes by chronic hypoxia, regardless of the training status of the animals, was previously observed in zebrafish gills (8) and in striated muscle of mice (9). The master regulator of cellular O 2 homeostasis, the hypoxia-inducible transcription factor 1 (HIF-1), has been implicated in the mouse for this transcriptional activation (9).…”

mentioning

confidence: 99%