title: Critical re-evaluation of neuroglobin expression reveals conserved patterns among mammals.
abstract: Neuroglobin (Ngb) is a respiratory protein that is almost exclusively expressed in the vertebrate nervous system. Despite many years of research, the exact function and even the expression sites of Ngb are still a matter of debate. However, to investigate hypotheses surrounding the potential roles of Ngb, a detailed knowledge of its major and minor expression sites is indispensable. We have therefore evaluated Ngb expression by extensive bioinformatic analysis using publicly available transcriptome data (RNA-Seq). During mammalian brain development, we observed low embryonic expression of Ngb mRNA and an increase after birth, arguing against a role of Ngb in fetal hypoxia tolerance. In adult mouse brain, we found highest Ngb mRNA levels in the hypothalamus, where expression was up to 100-fold stronger than in cerebral cortex, cerebellum or hippocampus, as confirmed by qRT-PCR and Western blotting. High Ngb expression in the hypothalamus was found conserved in humans and other mammals. Thus, Ngb mRNA is expressed at a basal level in many mammalian brain regions, but shows distinctive regional peaks. RNA-Seq analysis further revealed only low levels of Ngb mRNA in retina and testes and no signal in standard tumor cell lines, thus raising questions concerning previous studies and functional hypotheses. In conclusion, this broad-scale expression study may point to distinct Ngb functions for high- and low-expressing cells and tissues and argues against a single, generic role of Ngb as an oxygen supplier or as an endogenous protectant in all nerve cells.
authors.affiliation: Institute of Molecular Genetics, Johannes Gutenberg-University Mainz, D-55099 Mainz, Germany; Institute of Zoology, Biocenter Grindel, University of Hamburg, D-20146 Hamburg, Germany.
authors.forename: Andrej
authors.initials: A
authors.lastname: Fabrizius
authors.affiliation: Institute of Molecular Genetics, Johannes Gutenberg-University Mainz, D-55099 Mainz, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Andre
authors.affiliation: Institute of Molecular Genetics, Johannes Gutenberg-University Mainz, D-55099 Mainz, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Laufs
authors.affiliation: Institute of Molecular Genetics, Johannes Gutenberg-University Mainz, D-55099 Mainz, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Bicker
authors.affiliation: Department of Nuclear Medicine, University Medical Center, Johannes Gutenberg-University, Langenbeckstr. 1, D-55101 Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Reuss
authors.affiliation: Institute of Molecular Genetics, Johannes Gutenberg-University Mainz, D-55099 Mainz, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Porto
authors.affiliation: Institute of Zoology, Biocenter Grindel, University of Hamburg, D-20146 Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Burmester
authors.affiliation: Institute of Molecular Genetics, Johannes Gutenberg-University Mainz, D-55099 Mainz, Germany. Electronic address: hankeln@uni-mainz.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankeln
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D005914:Globins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D008322:Mammals; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000078787:Neuroglobin; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D012333:RNA, Messenger; D005914:Globins
keywords: Hypothalamus; RNA-Seq; mRNA expression