Publication:
Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL

dc.contributor.authorPlaisance, Valerie
dc.contributor.authorBrajkovic, Saska
dc.contributor.authorTenenbaum, Mathie
dc.contributor.authorFavre, Dimitri
dc.contributor.authorEzanno, Helene
dc.contributor.authorBonnefond, Amelie
dc.contributor.authorBonner, Caroline
dc.contributor.authorGmyr, Valery
dc.contributor.authorKerr-Conte, Julie
dc.contributor.authorGauthier, Benoit R.
dc.contributor.authorWidmann, Christian
dc.contributor.authorWaeber, Gerard
dc.contributor.authorPattou, Francois
dc.contributor.authorFroguel, Philippe
dc.contributor.authorAbderrahmani, Amar
dc.contributor.authoraffiliation[Plaisance, Valerie] Univ Lille, CNRS, Inst Pasteur Lille, UMR 8199 EGID, Lille, France
dc.contributor.authoraffiliation[Brajkovic, Saska] Univ Lille, CNRS, Inst Pasteur Lille, UMR 8199 EGID, Lille, France
dc.contributor.authoraffiliation[Tenenbaum, Mathie] Univ Lille, CNRS, Inst Pasteur Lille, UMR 8199 EGID, Lille, France
dc.contributor.authoraffiliation[Favre, Dimitri] Univ Lille, CNRS, Inst Pasteur Lille, UMR 8199 EGID, Lille, France
dc.contributor.authoraffiliation[Ezanno, Helene] Univ Lille, CNRS, Inst Pasteur Lille, UMR 8199 EGID, Lille, France
dc.contributor.authoraffiliation[Bonnefond, Amelie] Univ Lille, CNRS, Inst Pasteur Lille, UMR 8199 EGID, Lille, France
dc.contributor.authoraffiliation[Froguel, Philippe] Univ Lille, CNRS, Inst Pasteur Lille, UMR 8199 EGID, Lille, France
dc.contributor.authoraffiliation[Abderrahmani, Amar] Univ Lille, CNRS, Inst Pasteur Lille, UMR 8199 EGID, Lille, France
dc.contributor.authoraffiliation[Brajkovic, Saska] Univ Lausanne, Ctr Hosp Univ Vaudois, Serv Internal Med, Lausanne, Switzerland
dc.contributor.authoraffiliation[Favre, Dimitri] Univ Lausanne, Ctr Hosp Univ Vaudois, Serv Internal Med, Lausanne, Switzerland
dc.contributor.authoraffiliation[Waeber, Gerard] Univ Lausanne, Ctr Hosp Univ Vaudois, Serv Internal Med, Lausanne, Switzerland
dc.contributor.authoraffiliation[Bonner, Caroline] Univ Lille, INSERM, CHU Lille, U1190 EGID, Lille, France
dc.contributor.authoraffiliation[Gmyr, Valery] Univ Lille, INSERM, CHU Lille, U1190 EGID, Lille, France
dc.contributor.authoraffiliation[Kerr-Conte, Julie] Univ Lille, INSERM, CHU Lille, U1190 EGID, Lille, France
dc.contributor.authoraffiliation[Pattou, Francois] Univ Lille, INSERM, CHU Lille, U1190 EGID, Lille, France
dc.contributor.authoraffiliation[Gauthier, Benoit R.] Andalusian Ctr Mol Biol & Regenerat Med, Dept Stem Cells, Seville, Spain
dc.contributor.authoraffiliation[Widmann, Christian] Univ Lausanne, Dept Physiol, Lausanne, Switzerland
dc.contributor.authoraffiliation[Bonnefond, Amelie] Imperial Coll London, Dept Genom Common Dis, London, England
dc.contributor.authoraffiliation[Froguel, Philippe] Imperial Coll London, Dept Genom Common Dis, London, England
dc.contributor.authoraffiliation[Abderrahmani, Amar] Imperial Coll London, Dept Genom Common Dis, London, England
dc.contributor.funder"European Genomic Institute for Diabetes" (E.G.I.D.)
dc.contributor.funderEuropean Commission
dc.contributor.funderRegional Council Nord Pas de Calais
dc.contributor.funderEuropean Regional Development Fund
dc.date.accessioned2023-02-12T02:22:20Z
dc.date.available2023-02-12T02:22:20Z
dc.date.issued2016-09-16
dc.description.abstractElevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1a, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/ CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment.
dc.identifier.doi10.1371/journal.pone.0163046
dc.identifier.issn1932-6203
dc.identifier.unpaywallURLhttps://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0163046&type=printable
dc.identifier.urihttp://hdl.handle.net/10668/19161
dc.identifier.wosID383723700029
dc.issue.number9
dc.journal.titlePlos one
dc.journal.titleabbreviationPlos one
dc.language.isoen
dc.organizationCentro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER
dc.publisherPublic library science
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectUnfolded protein response
dc.subjectDiabetes-mellitus
dc.subjectDensity-lipoproteins
dc.subjectEr stress
dc.subjectMacrophages
dc.subjectApoptosis
dc.subjectAntioxidants
dc.subjectMetabolism
dc.subjectActivation
dc.subjectExpression
dc.titleEndoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number11
dc.wostypeArticle
dspace.entity.typePublication

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