RT Journal Article
T1 Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL
A1 Plaisance, Valerie
A1 Brajkovic, Saska
A1 Tenenbaum, Mathie
A1 Favre, Dimitri
A1 Ezanno, Helene
A1 Bonnefond, Amelie
A1 Bonner, Caroline
A1 Gmyr, Valery
A1 Kerr-Conte, Julie
A1 Gauthier, Benoit R.
A1 Widmann, Christian
A1 Waeber, Gerard
A1 Pattou, Francois
A1 Froguel, Philippe
A1 Abderrahmani, Amar
K1 Unfolded protein response
K1 Diabetes-mellitus
K1 Density-lipoproteins
K1 Er stress
K1 Macrophages
K1 Apoptosis
K1 Antioxidants
K1 Metabolism
K1 Activation
K1 Expression
AB 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.
PB Public library science
SN 1932-6203
YR 2016
FD 2016-09-16
LK http://hdl.handle.net/10668/19161
UL http://hdl.handle.net/10668/19161
LA en
DS RISalud
RD Apr 20, 2025