Regulation and Role of Neuroglobin and Cytoglobin Under Hypoxia

Burmester, Thorsten; Gerlach, Frank; Hankeln, Thomas

doi:10.1007/978-0-387-75434-5_13

Cited by 82 publications

(73 citation statements)

References 32 publications

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“…Cytoglobin, the gene involved in cell proliferation _ possibly via collagen synthesis _ and expressed predominantly in fibroblasts and associated cell types, is significantly elevated under hypoxic conditions (12). In this study, cytoglobin was upregulated in both the liver and CCl 4 liver groups.…”

Section: Discussionsupporting

confidence: 47%

Gene expression profile of mesenchymal stromal cells after co-culturing with injured liver tissue

Woo¹

2008

Mol Med Rep

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Abstract. Mesenchymal stromal cells (MSCs) are a potential cell source for the development of therapeutic products. Recent studies have shown that the transplantation of MSCs to damaged organs, including the heart, liver and kidneys, results in the restoration of the damaged tissues. However, the mechanisms underlying this regeneration process have yet to be clearly characterized. Consequently, in this study, we focused on the therapeutic potential of MSCs in injured liver tissue by evaluating the gene expression profiles of MSCs in the presence of injured liver and normal liver cells using a microarray chip containing 44,000 genes. In order to mimic the state of liver cell regeneration in vitro, we respectively cocultured MSCs with CCl 4 -injured liver cells and normal liver cells from C57BL/6 female mice. After 48 h of co-culturing, MSCs were collected and the RNA was extracted for microarray analysis. Under conditions of co-culture with normal liver cells, upregulated expression of CXCR6, CCR3, IL-2, IL-11, CD34, CD74, procollagen, FMS-like tyrosine kinase, neuregulin 4, Wnt2 and catenins was noted. Under conditions of co-culture with the CCl 4 -injured liver cells, expression of CXCL2, cytoglobin, erythropoietin, v-Erb, hypoxia-inducible factor 3 (· subunit), retinoic acid receptor ß and Vav2 was upregulated. Our research provides information regarding the differential molecular mechanisms that regulate the properties of MSCs in the regeneration of injured liver tissue.

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Section: Discussionsupporting

confidence: 47%

Gene expression profile of mesenchymal stromal cells after co-culturing with injured liver tissue

Woo¹

2008

Mol Med Rep

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“…If Ngb is associated with O 2 consumption, it may be expected that alterations of external O 2 supply may also affect Ngb expression (for review, see Burmester et al, 2007). In cell culture systems, Ngb expression may actually be moderately induced by hypoxia (Schmidt-Kastner et al, 2006;Sun et al, 2001).…”

Section: Hypoxia Regulation Of Ngbmentioning

confidence: 99%

“…However, it must be considered that under non-pathological conditions most terrestrial mammals will never experience hypoxic phases during their adult life. Therefore, it is unlikely that their nervous systems are well adapted to O 2 shortage and that Ngb expression responds to hypoxia (Burmester et al, 2007). By contrast, certain fish species and aquatic turtles live in environments with low O 2 availability.…”

Section: Hypoxia Regulation Of Ngbmentioning

confidence: 99%

What is the function of neuroglobin?

Burmester¹,

Hankeln

2009

Journal of Experimental Biology

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224

215

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SUMMARY For a long time, haemoglobin and myoglobin had been assumed to represent the only globin types of vertebrates. In 2000, however, we discovered a third globin type by mining the genome sequence data. Based on a preferential expression in the nervous system, this globin is referred to as neuroglobin. Despite nine years of research, its function is still uncertain and a number of hypotheses have been put forward. Neuroglobin enhances cell viability under hypoxia and under various types of oxidative stress in transgenic systems, but does not appear to be strongly upregulated in response to stress. A close phylogenetic relationship with invertebrate nerve globins and its positive correlation with the oxidative metabolism and mitochondria suggest a role in O2 supply. In vitro studies and cell culture experiments imply that neuroglobin may detoxify reactive oxygen or nitric oxide. Still other studies propose neuroglobin as being part of a signalling chain that transmits the redox state of the cell or that inhibits apoptosis. Although some functions are more probable than others, we conclude that it is still too early to definitively decide what may be the physiological role(s) of neuroglobin in vertebrates. Nevertheless, there is no doubt that neuroglobin has an essential, conserved function and is beneficial to neurons.

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“…The function of Cygb is even less clear than that of Ngb but has been interpreted in terms of ROS defense or O 2 supply to certain enzymes (17,33,35).…”

mentioning

confidence: 99%

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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Regulation and Role of Neuroglobin and Cytoglobin Under Hypoxia

Cited by 82 publications

References 32 publications

Gene expression profile of mesenchymal stromal cells after co-culturing with injured liver tissue

Gene expression profile of mesenchymal stromal cells after co-culturing with injured liver tissue

What is the function of neuroglobin?

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

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