Cellular protection from oxidative DNA damage by over-expression of the novel globin cytoglobin in vitro

Abstract

Cytoglobin is a recently identified member of the mammalian globin family that is expressed in neuronal cells in the central and peripheral nervous system where its physiological role remains to be determined. In the current study, we demonstrate that a cytoglobin-green fluoresecent protein (GFP) fusion protein when expressed in the human neuronal cell line TE671 has a nuclear localization in a subpopulation of transfected cells (approximately 15%). Furthermore, the cytoglobin-GFP fusion protein but not GFP alone significantly reduced the induction of intracellular reactive oxygen species as assessed by oxidation of the redox-sensitive probe dichlorofluorescein following treatment with non-cytotoxic concentrations of the pro-oxidant Ro19-8022. In addition, expression of cytoglobin-GFP also afforded cytoprotection from Ro19-8022-induced oxidative DNA damage as assessed by the Fpg-modified comet assay. In conclusion, the current study provides evidence supportive of a role for cytoglobin in cytoprotection of neuronal cells from oxidative-related damage, for example, during ischaemic reperfusion injury following hypoxia.

Promotion of Liver and Lung Tumorigenesis in DEN-Treated Cytoglobin-Deficient Mice

“…8,9 In contrast, CYGB overexpression rescues the human neuronal cell line TE671 from prooxidant Ro19-8022-induced DNA damage. 10 CYGB overexpression also protected human neuroblastoma SH-SY5Y cells from H 2 O 2 -induced cell death. 11,12 Furthermore, the in vitro and in vivo overexpression of Cygb in rat hepatic stellate cells protected these cells against oxidative stress and inhibited their differentiation into an active phenotype.…”

Neurochemical phenotype of cytoglobin-expressing neurons in the rat hippocampus

“…The Cygb expression patterns in the mouse brain were recently determined to be identical in the rat and human brain, demonstrating that the rodent brain can be used as a translational model for studying Cygb in humans, at least at the anatomical level (12,13). The function of Cygb remains largely unknown, but several studies have linked Cygb to reactive oxygen/nitrogen species (RNS) nitric oxide (NO) scavenging (14)(15)(16)(17)(18)(19)(20). Furthermore, Cygb overexpression protects against ischemic cell death in vivo (21), although not when expressed at endogenous levels (22).…”

Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer

“…The exact physiological role of Cygb is currently speculative, although intracellular oxygen storage, peroxidase function, oxygen sensing or binding and detoxification of nitric oxide have all been suggested (Burmester et al, 2002(Burmester et al, , 2004Trent III and Hargrove, 2002;Hankeln et al, 2005;Hodges et al, 2008). It has been recently shown that upregulation of CYGB in rat liver cells has a protective effect against damage-induced fibrosis (Xu et al, 2006) and this has led to the hypothesis that CYGB has a homoeostatic effect, inhibiting free radical-induced fibroblast activation and consequent fibrosis.…”