title: Protection from intracellular oxidative stress by cytoglobin in normal and cancerous oesophageal cells.
abstract: Cytoglobin is an intracellular globin of unknown function that is expressed mostly in cells of a myofibroblast lineage. Possible functions of cytoglobin include buffering of intracellular oxygen and detoxification of reactive oxygen species. Previous work in our laboratory has demonstrated that cytoglobin affords protection from oxidant-induced DNA damage when over expressed in vitro, but the importance of this in more physiologically relevant models of disease is unknown. Cytoglobin is a candidate for the tylosis with oesophageal cancer gene, and its expression is strongly down-regulated in non-cancerous oesophageal biopsies from patients with TOC compared with normal biopsies. Therefore, oesophageal cells provide an ideal experimental model to test our hypothesis that downregulation of cytoglobin expression sensitises cells to the damaging effects of reactive oxygen species, particularly oxidative DNA damage, and that this could potentially contribute to the TOC phenotype. In the current study, we tested this hypothesis by manipulating cytoglobin expression in both normal and oesophageal cancer cell lines, which have normal physiological and no expression of cytoglobin respectively. Our results show that, in agreement with previous findings, over expression of cytoglobin in cancer cell lines afforded protection from chemically-induced oxidative stress but this was only observed at non-physiological concentrations of cytoglobin. In addition, down regulation of cytoglobin in normal oesophageal cells had no effect on their sensitivity to oxidative stress as assessed by a number of end points. We therefore conclude that normal physiological concentrations of cytoglobin do not offer cytoprotection from reactive oxygen species, at least in the current experimental model.
authors.affiliation: School of Biosciences, The University of Birmingham, Edgbaston, Birmingham, United Kingdom.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: McRonald
authors.forename: Janet M
authors.initials: JM
authors.lastname: Risk
authors.forename: Nikolas J
authors.initials: NJ
authors.lastname: Hodges
mesh_terms: D000078842:Cytoglobin; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015870:Gene Expression; D005914:Globins / Q000494:pharmacology*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D014407:Tumor Cells, Cultured
chemical_list: C000627265:CYGB protein, human; D000078842:Cytoglobin; D017382:Reactive Oxygen Species; D005914:Globins