Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL.
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 str...
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doaj-9e162419a61946c3a22b52e90a921f802020-11-25T01:55:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016304610.1371/journal.pone.0163046Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL.Valérie PlaisanceSaška BrajkovicMathie TenenbaumDimitri FavreHélène EzannoAmélie BonnefondCaroline BonnerValéry GmyrJulie Kerr-ConteBenoit R GauthierChristian WidmannGérard WaeberFrançois PattouPhilippe FroguelAmar AbderrahmaniElevated 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.http://europepmc.org/articles/PMC5026355?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valérie Plaisance Saška Brajkovic Mathie Tenenbaum Dimitri Favre Hélène Ezanno Amélie Bonnefond Caroline Bonner Valéry Gmyr Julie Kerr-Conte Benoit R Gauthier Christian Widmann Gérard Waeber François Pattou Philippe Froguel Amar Abderrahmani |
spellingShingle |
Valérie Plaisance Saška Brajkovic Mathie Tenenbaum Dimitri Favre Hélène Ezanno Amélie Bonnefond Caroline Bonner Valéry Gmyr Julie Kerr-Conte Benoit R Gauthier Christian Widmann Gérard Waeber François Pattou Philippe Froguel Amar Abderrahmani Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL. PLoS ONE |
author_facet |
Valérie Plaisance Saška Brajkovic Mathie Tenenbaum Dimitri Favre Hélène Ezanno Amélie Bonnefond Caroline Bonner Valéry Gmyr Julie Kerr-Conte Benoit R Gauthier Christian Widmann Gérard Waeber François Pattou Philippe Froguel Amar Abderrahmani |
author_sort |
Valérie Plaisance |
title |
Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL. |
title_short |
Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL. |
title_full |
Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL. |
title_fullStr |
Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL. |
title_full_unstemmed |
Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL. |
title_sort |
endoplasmic reticulum stress links oxidative stress to impaired pancreatic beta-cell function caused by human oxidized ldl. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC5026355?pdf=render |
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