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dc.contributor.authorFerguson, Daniel CJ
dc.contributor.authorSmerdon, Gary R
dc.contributor.authorHarries, Lorna W
dc.contributor.authorDodd, Nicholas JF
dc.contributor.authorMurphy, Mike
dc.contributor.authorCurnow, Alison
dc.contributor.authorWinyard, Paul G
dc.date.accessioned2018-11-22T00:33:22Z
dc.date.available2018-11-22T00:33:22Z
dc.date.issued2018-10
dc.identifier.issn0891-5849
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285697
dc.description.abstractIn vivo, mammalian cells reside in an environment of 0.5-10% O2 (depending on the tissue location within the body), whilst standard in vitro cell culture is carried out under room air. Little is known about the effects of this hyperoxic environment on treatment-induced oxidative stress, relative to a physiological oxygen environment. In the present study we investigated the effects of long-term culture under hyperoxia (air) on photodynamic treatment. Upon photodynamic irradiation, cells which had been cultured long-term under hyperoxia generated higher concentrations of mitochondrial reactive oxygen species, compared with cells in a physioxic (2% O2) environment. However, there was no significant difference in viability between hyperoxic and physioxic cells. The expression of genes encoding key redox homeostasis proteins and the activity of key antioxidant enzymes was significantly higher after the long-term culture of hyperoxic cells compared with physioxic cells. The induction of antioxidant genes and increased antioxidant enzyme activity appear to contribute to the development of a phenotype that is resistant to oxidative stress-induced cellular damage and death when using standard cell culture conditions. The results from experiments using selective inhibitors suggested that the thioredoxin antioxidant system contributes to this phenotype. To avoid artefactual results, in vitro cellular responses should be studied in mammalian cells that have been cultured under physioxia. This investigation provides new insights into the effects of physioxic cell culture on a model of a clinically relevant photodynamic treatment and the associated cellular pathways.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectMitochondria
dc.subjectAnimals
dc.subjectHumans
dc.subjectHyperoxia
dc.subjectOxygen
dc.subjectReactive Oxygen Species
dc.subjectPhotochemotherapy
dc.subjectCell Culture Techniques
dc.subjectOxidation-Reduction
dc.subjectHomeostasis
dc.subjectMetabolic Networks and Pathways
dc.titleAltered cellular redox homeostasis and redox responses under standard oxygen cell culture conditions versus physioxia.
dc.typeArticle
prism.endingPage333
prism.publicationDate2018
prism.publicationNameFree Radic Biol Med
prism.startingPage322
prism.volume126
dc.identifier.doi10.17863/CAM.33047
dcterms.dateAccepted2018-08-20
rioxxterms.versionofrecord10.1016/j.freeradbiomed.2018.08.025
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-10
dc.contributor.orcidMurphy, Mike [0000-0003-1115-9618]
dc.identifier.eissn1873-4596
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_UU_00015/3)
pubs.funder-project-idWellcome Trust (110159/Z/15/Z)


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Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International