Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia
Open accessAbstract
Cytoglobin is a recently discovered vertebrate globin distantly related to myoglobin, and its function is unknown. Here we present the first detailed analysis of the distribution and expression of cytoglobin. Northern and Western blotting experiments show the presence of cytoglobin mRNA and protein in a broad range of tissues. Quantitative PCR demonstrates an up-regulation of cytoglobin mRNA levels in rat heart and liver under hypoxic conditions (22 and 44 h of 9% oxygen). Immunofluorescence studies with three antibodies directed against different epitopes of the protein consistently show cytoglobin in connective tissue fibroblasts as well as in hepatic stellate cells. Cytoglobin is also present in chondroblasts and osteoblasts and shows a decreased level of expression upon differentiation to chondrocytes and osteocytes. Cytoglobin is located in the cytoplasm of these cell types. Evidence against an exclusively nuclear localization of cytoglobin, as recently proposed, is also provided by transfection assays with green fluorescent protein fusion constructs, which demonstrates the absence of an active nuclear import. The differential expression of cytoglobin argues against a general respiratory function of this molecule, but rather indicates a connective tissue-specific function. We hypothesize that cytoglobin may be involved in collagen synthesis. Cytoglobin expression was also observed in some neuronal subpopulations of the central and the peripheral nervous systems. Surprisingly, cytoglobin is localized in both the cytoplasm and nucleus of neurons, indicating a possible additional role of this protein in neuronal tissues.
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Cytoglobin is found in micromolar concentrations but can be increased about 10-fold under hypoxic conditions.
“Cytoglobin is found in micromolar concentrations but can be increased about 10-fold under hypoxic conditions [75].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [75]
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Gene expression during chemically induced liver fibrosis: effect of halofuginone on TGF-β signaling
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A Membrane-Bound Vertebrate Globin
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Neuroglobin of seals and whales: Evidence for a divergent role in the diving brain
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The globin gene family of the cephalochordate amphioxus: implications for chordate globin evolution
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Mammalian nerve globins in search of functions
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Electrochemical Detection of Hemoglobin: A Review
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Running, swimming and diving modifies neuroprotecting globins in the mammalian brain
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Cytoglobin, a novel globin, plays an antifibrotic role in the kidney
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Identification of markers for quiescent pancreatic stellate cells in the normal human pancreas
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Respiratory Physiology of Vertebrates
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Divergent distribution of cytoglobin and neuroglobin in the murine eye
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Cytoglobin has bimodal: tumour suppressor and oncogene functions in lung cancer cell lines
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Brain globins in physiology and pathology
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Study of the hypoxia-dependent regulation of human CYGB gene
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Neuroglobin and cytoglobin: Two new entries in the hemoglobin superfamily*
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Duplicated cytoglobin genes in teleost fishes
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Emerging perspectives on cytoglobin, beyond NO dioxygenase and peroxidase
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Calcineurin Activates Cytoglobin Transcription in Hypoxic Myocytes
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Mechanisms of the protective effects of nitrate and nitrite in cardiovascular and metabolic diseases
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- Authors
- Schmidt, M., Gerlach, F., Avivi, A., Laufs, T., Wystub, S., Simpson, J. C., Nevo, E., Saaler-Reinhardt, S., Reuss, S., Hankeln, T., & Burmester, T.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- University of Haifa (IL)
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Burmester, Thorsten
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 279
- Issue
- 9
- Pages
- 8063-8069
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2099711702
- Cited by
- 222
- References
- 42
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 10 · 2022: 4 · 2021: 2 · 2020: 8 · 2019: 4 · 2018: 7 · 2017: 10 · 2016: 8 · 2015: 13 · 2014: 16 · 2013: 13 · 2012: 12
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Surgery › Biomedical and Chemical Research
- Keywords
- cytoglobin, globin, hypoxia, respiratory proteins, connective tissue, fibroblasts, hepatic stellate cells, chondroblasts, osteoblasts, chondrogenic differentiation, osteocyte differentiation, collagen synthesis, neuronal expression, nuclear import, tissue distribution
- MeSH terms
- Cytoglobin, Amino Acid Sequence, Animals, Hypoxia, Antibodies, Antibody Specificity, Bone and Bones, Cell Nucleus, Chlorocebus aethiops, Connective Tissue, Cytoplasm, Fibroblasts, Fluorescent Antibody Technique, Gene Expression Regulation, Globins, HeLa Cells, Humans, Immunohistochemistry, Liver, Luminescent Proteins, Mice, Inbred BALB C, Molecular Sequence Data, Myocardium, Neurons, Nuclear Proteins, Oxygen, Peptide Fragments, Recombinant Fusion Proteins, Respiratory System, RNA, Messenger, Trachea, Transfection, Vero Cells, Reverse Transcriptase Polymerase Chain Reaction, Green Fluorescent Proteins, Mice, Rats
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