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dc.contributor.authorBarlow, Jen
dc.contributor.authorHirschberg Jensen, Ven
dc.contributor.authorAffourtit, Cen
dc.date.accessioned2015-07-09T08:11:20Z
dc.date.available2015-07-09T08:11:20Z
dc.date.issued2015en
dc.identifier.urihttp://hdl.handle.net/10026.1/3417
dc.description.abstract

High glucose and fatty acid levels impair pancreatic beta cell function. We have recently shown that palmitate-induced loss of INS-1E insulinoma cells is related to increased reactive oxygen species (ROS) production as both toxic effects are prevented by palmitoleate. Here we show that palmitate-induced ROS are mostly mitochondrial: oxidation of MitoSOX, a mitochondria-targeted superoxide probe, is increased by palmitate, whilst oxidation of the equivalent non-targeted probe is unaffected. Moreover, mitochondrial respiratory inhibition with antimycin A stimulates palmitate-induced MitoSOX oxidation. We also show that palmitate does not change the level of mitochondrial uncoupling protein-2 (UCP2) and that UCP2 knockdown does not affect palmitate-induced MitoSOX oxidation. Palmitoleate does not influence MitoSOX oxidation in INS-1E cells ±UCP2 and largely prevents the palmitate-induced effects. Importantly, UCP2 knockdown amplifies the preventive effect of palmitoleate on palmitate-induced ROS. Consistently, viability effects of palmitate and palmitoleate are similar between cells ±UCP2, but UCP2 knockdown significantly augments the palmitoleate protection against palmitate-induced cell loss at high glucose. We conclude that UCP2 neither mediates palmitate-induced mitochondrial ROS generation and the associated cell loss, nor protects against these deleterious effects. Instead, UCP2 dampens palmitoleate protection against palmitate toxicity.

en
dc.format.extent14 - 22en
dc.languageengen
dc.language.isoengen
dc.subjectCytoprotectionen
dc.subjectGlucolipotoxicityen
dc.subjectINS-1E insulinoma cellsen
dc.subjectMitochondrial dysfunctionen
dc.subjectNon-esterified fatty acidsen
dc.subjectObesityen
dc.subjectPancreatic beta cellsen
dc.subjectReactive oxygen speciesen
dc.subjectType 2 diabetesen
dc.subjectUncoupling protein-2 (UCP2)en
dc.subjectAntimycin Aen
dc.subjectCell Counten
dc.subjectCell Line, Tumoren
dc.subjectFatty Acids, Monounsaturateden
dc.subjectGlucoseen
dc.subjectHumansen
dc.subjectInsulinen
dc.subjectInsulin-Secreting Cellsen
dc.subjectInsulinomaen
dc.subjectIon Channelsen
dc.subjectMitochondriaen
dc.subjectMitochondrial Proteinsen
dc.subjectOxidation-Reductionen
dc.subjectPancreatic Neoplasmsen
dc.subjectReactive Oxygen Speciesen
dc.subjectUncoupling Protein 2en
dc.titleUncoupling protein-2 attenuates palmitoleate protection against the cytotoxic production of mitochondrial reactive oxygen species in INS-1E insulinoma cells.en
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/25482405en
plymouth.volume4en
plymouth.publication-statusPublisheden
plymouth.journalRedox Biolen
dc.identifier.doi10.1016/j.redox.2014.11.009en
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/00 Groups by role
plymouth.organisational-group/Plymouth/00 Groups by role/Academics
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group/RC Reporting Group BRG
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
dc.publisher.placeNetherlandsen
dcterms.dateAccepted2014-11-24en
dc.identifier.eissn2213-2317en
dc.rights.embargoperiodNo embargoen
rioxxterms.versionofrecord10.1016/j.redox.2014.11.009en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015en
rioxxterms.typeJournal Article/Reviewen
plymouth.funderWhy do pancreatic beta cells waste energy?::MRCen


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