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dc.contributor.authorAdemowo, Opeyemi S.
dc.contributor.authorDias, Irundika H.K.
dc.contributor.authorDiaz-Sanchez, Lorena
dc.contributor.authorSanchez-Aranguren, Lissette
dc.contributor.authorStahl, Wilhelm
dc.contributor.authorGriffiths, Helen R.
dc.date.accessioned2020-03-05T09:40:39Z
dc.date.available2020-03-05T09:40:39Z
dc.date.issued2020-01-20
dc.identifier.citationAdemowo, O.S., Dias, I.H., Diaz-Sanchez, L., Sanchez-Aranguren, L., Stahl, W. and Griffiths, H.R., (2020). 'Partial mitigation of oxidized phospholipid-mediated mitochondrial dysfunction in neuronal cells by oxocarotenoids'. Journal of Alzheimer's Disease, pp. 1-14. DOI: 10.3233/jad-190923en_US
dc.identifier.issn1387-2877
dc.identifier.doi10.3233/jad-190923
dc.identifier.urihttp://hdl.handle.net/10545/624543
dc.description.abstractMitochondria are important (patho)physiological sources of reactive oxygen species (ROS) that mediate mitochondrial dysfunction and phospholipid oxidation; an increase in mitochondrial content of oxidized phospholipid (OxPL) associates with cell death. Previously we showed that the circulating OxPL 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) increases in patients with Alzheimer's disease (AD), and associates with lower plasma antioxidant oxocarotenoids, zeaxanthin, and lutein. Since oxocarotenoids are metabolized in mitochondria, we propose that during AD, lower concentrations of mitochondrial zeaxanthin and lutein may result in greater phospholipid oxidation and predispose to neurodegeneration. Here, we have investigated whether non-toxic POVPC concentrations impair mitochondrial metabolism in differentiated (d)SH-SY5Y neuronal cells and whether there is any protective role for oxocarotenoids against mitochondrial dysfunction. After 24 hours, glutathione (GSH) concentration was lower in neuronal cells exposed to POVPC (1-20μM) compared with vehicle control without loss of viability compared to control. However, mitochondrial ROS production (determined by MitoSOX oxidation) was increased by 50% only after 20μM POVPC. Following delivery of lutein (0.1-1μM) and zeaxanthin (0.5-5μM) over 24 hours in vitro, oxocarotenoid recovery from dSH-SY5Y cells was > 50%. Co-incubation with oxocarotenoids prevented loss of GSH after 1μM but not 20μM POVPC, whereas the increase in ROS production induced by 20μM POVPC was prevented by lutein and zeaxanthin. Mitochondrial uncoupling increases and ATP production is inhibited by 20μM but not 1μM POVPC; carotenoids protected against uncoupling although did not restore ATP production. In summary, 20μM POVPC induced loss of GSH and a mitochondrial bioenergetic deficit in neuronal cells that was not mitigated by oxocarotenoids.en_US
dc.description.sponsorshipOSA was supported by the Aston Research Centre for Healthy Ageing. HKID and HRG gratefully acknowledge support from the Kidney Research Foundation PDF3/2014. HKID also acknowledges support from Alzheimer's Research UK network grant LES811839.en_US
dc.language.isoenen_US
dc.publisherIOS Pressen_US
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/31985464en_US
dc.relation.urlhttps://pure.aston.ac.uk/ws/portalfiles/portal/37369493/Partial_Mitigation_of_Oxidized.pdfen_US
dc.relation.urlhttps://content.iospress.com/articles/journal-of-alzheimers-disease/jad190923en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectBioenergeticsen_US
dc.subjectPOVPCen_US
dc.subjectCarotenoidsen_US
dc.subjectLuteinen_US
dc.subjectMitochondriaen_US
dc.subjectOxidative stressen_US
dc.subjectOxidized phospholipidsen_US
dc.subjectViabilityen_US
dc.subjectZeaxanthin.en_US
dc.titlePartial mitigation of oxidized phospholipid-mediated mitochondrial dysfunction in neuronal cells by oxocarotenoidsen_US
dc.title.alternativeCarotenoids and mitochondrial functionen_US
dc.typeArticleen_US
dc.identifier.eissn1875-8908
dc.contributor.departmentAston University, Birmingham, West Midlands, UKen_US
dc.contributor.departmentInstitute of Biochemistry and Molecular Biology, Germanyen_US
dc.contributor.departmentUniversity of Surreyen_US
dc.identifier.journalJournal of Alzheimer's Diseaseen_US
dc.source.journaltitleJournal of Alzheimer's Disease
dc.source.beginpage1
dc.source.endpage14
dcterms.dateAccepted2019-12-20
dc.author.detail300514en_US


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