Publication: Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL
dc.contributor.author | Plaisance, Valerie | |
dc.contributor.author | Brajkovic, Saska | |
dc.contributor.author | Tenenbaum, Mathie | |
dc.contributor.author | Favre, Dimitri | |
dc.contributor.author | Ezanno, Helene | |
dc.contributor.author | Bonnefond, Amelie | |
dc.contributor.author | Bonner, Caroline | |
dc.contributor.author | Gmyr, Valery | |
dc.contributor.author | Kerr-Conte, Julie | |
dc.contributor.author | Gauthier, Benoit R. | |
dc.contributor.author | Widmann, Christian | |
dc.contributor.author | Waeber, Gerard | |
dc.contributor.author | Pattou, Francois | |
dc.contributor.author | Froguel, Philippe | |
dc.contributor.author | Abderrahmani, 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.funder | European Commission | |
dc.contributor.funder | Regional Council Nord Pas de Calais | |
dc.contributor.funder | European Regional Development Fund | |
dc.date.accessioned | 2023-02-12T02:22:20Z | |
dc.date.available | 2023-02-12T02:22:20Z | |
dc.date.issued | 2016-09-16 | |
dc.description.abstract | Elevated 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.doi | 10.1371/journal.pone.0163046 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.unpaywallURL | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0163046&type=printable | |
dc.identifier.uri | http://hdl.handle.net/10668/19161 | |
dc.identifier.wosID | 383723700029 | |
dc.issue.number | 9 | |
dc.journal.title | Plos one | |
dc.journal.titleabbreviation | Plos one | |
dc.language.iso | en | |
dc.organization | Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER | |
dc.publisher | Public library science | |
dc.rights | Attribution 4.0 International | |
dc.rights.accessRights | open access | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Unfolded protein response | |
dc.subject | Diabetes-mellitus | |
dc.subject | Density-lipoproteins | |
dc.subject | Er stress | |
dc.subject | Macrophages | |
dc.subject | Apoptosis | |
dc.subject | Antioxidants | |
dc.subject | Metabolism | |
dc.subject | Activation | |
dc.subject | Expression | |
dc.title | Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL | |
dc.type | research article | |
dc.type.hasVersion | VoR | |
dc.volume.number | 11 | |
dc.wostype | Article | |
dspace.entity.type | Publication |