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

  • Plaisance V Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France.
  • Brajkovic S Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France.
  • Tenenbaum M Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France.
  • Favre D Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France.
  • Ezanno H Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France.
  • Bonnefond A Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France.
  • Bonner C Univ. Lille, Inserm, CHU Lille, U1190 - EGID, Lille, France.
  • Gmyr V Univ. Lille, Inserm, CHU Lille, U1190 - EGID, Lille, France.
  • Kerr-Conte J Univ. Lille, Inserm, CHU Lille, U1190 - EGID, Lille, France.
  • Gauthier BR Department of Stem Cells, Andalusian Center for Molecular Biology and Regenerative Medicine, Seville, Spain.
  • Widmann C Department of Physiology, Lausanne University, Lausanne, Switzerland.
  • Waeber G Service of Internal Medicine, Centre Hospitalier Universitaire Vaudois and Lausanne University, Lausanne, Switzerland.
  • Pattou F Univ. Lille, Inserm, CHU Lille, U1190 - EGID, Lille, France.
  • Froguel P Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France.
  • Abderrahmani A Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8199 - EGID, Lille, France.
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  • 2016-09-17
Published in:
  • PloS one. - 2016
Acetylcysteine
Activating Transcription Factor 6
Animals
Antioxidants
Apoptosis
Biomarkers
Cell Line
Endoplasmic Reticulum Stress
Endoribonucleases
Humans
Hydrogen Peroxide
Insulin
Islets of Langerhans
Lipoproteins, LDL
Mice
Oxidative Stress
Protein-Serine-Threonine Kinases
English 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.
Language
  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/25358
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