Cited by 222Hemoglobin structure and functionHeme Oxygenase-1 and Carbon MonoxideBiomedical and Chemical Research

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Cytoglobin Is a Respiratory Protein in Connective Tissue and Neurons, Which Is Up-regulated by Hypoxia

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Schmidt, Marc, Gerlach, Frank, Avivi, Aaron, Laufs, Tilmann, Wystub, Sylvia, Simpson, Jeremy C., Nevo, Eviatar, Saaler-Reinhardt, Sigrid, Reuss, Stefan, Hankeln, Thomas, Burmester, Thorsten·2004·Journal of Biological Chemistry

DOI 10.1074/jbc.m310540200

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Abstract

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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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: Schmidt, Marc
Avivi, Aaron
Simpson, Jeremy C.
Nevo, Eviatar
Reuss, Stefan
Hankeln, Thomas
Burmester, Thorsten
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2004-02
Volume: 279
Issue: 9
Pages: 8063-8069
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m310540200
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6100 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Health Sciences › Medicine › Physiology (medical) › 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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Cytoglobin Is a Respiratory Protein in Connective Tissue and Neurons, Which Is Up-regulated by Hypoxia

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