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

Détails

Ressource 1Télécharger: journal.pone.0163046.PDF (1606.64 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_02DE13CCAB6C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL.
Périodique
PloS one
Auteur(s)
Plaisance V., Brajkovic S., Tenenbaum M., Favre D., Ezanno H., Bonnefond A., Bonner C., Gmyr V., Kerr-Conte J., Gauthier B.R., Widmann C., Waeber G., Pattou F., Froguel P., Abderrahmani A.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
11
Numéro
9
Pages
e0163046
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
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 1α, 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.

Pubmed
Web of science
Open Access
Oui
Création de la notice
28/09/2016 17:33
Dernière modification de la notice
20/08/2019 12:24
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