1. HDLs Protect Pancreatic β-Cells Against ER Stress by Restoring Protein Folding and Trafficking
- Author
-
Christian Widmann, Florent Allagnat, Jean-Christophe Jonas, Gérard Waeber, Miguel Frias, Jean-Yves Chatton, Jannick Pétremand, Jessica Duprez, Richard W. James, and Julien Puyal
- Subjects
Male ,Protein Folding ,Endocrinology, Diabetes and Metabolism ,Apoptosis ,Insulinoma/metabolism ,Endoplasmic Reticulum ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Stress, Physiological/physiology ,Insulin-Secreting Cells ,Endoplasmic Reticulum/physiology ,Cells, Cultured ,ddc:616 ,0303 health sciences ,Lipoproteins, HDL/genetics/metabolism ,Brefeldin A ,3. Good health ,Cell biology ,Transport protein ,Protein Transport ,Animals ,Green Fluorescent Proteins/metabolism ,Humans ,Insulin-Secreting Cells/cytology ,Insulin-Secreting Cells/metabolism ,Lipoproteins, HDL/genetics ,Lipoproteins, HDL/metabolism ,Membrane Proteins/metabolism ,Mutation ,Rats ,Rats, Wistar ,Viral Fusion Proteins/metabolism ,symbols ,Lipoproteins, HDL ,Signal Transduction ,medicine.medical_specialty ,Thapsigargin ,Green Fluorescent Proteins ,030209 endocrinology & metabolism ,Biology ,03 medical and health sciences ,symbols.namesake ,Stress, Physiological ,Insulin-Secreting Cells/cytology/metabolism/ultrastructure ,Internal medicine ,Internal Medicine ,medicine ,030304 developmental biology ,Endoplasmic reticulum ,Membrane Proteins ,Golgi apparatus ,Endocrinology ,chemistry ,Unfolded protein response ,Insulinoma ,Viral Fusion Proteins ,Homeostasis - Abstract
Endoplasmic reticulum (ER) homeostasis alteration contributes to pancreatic β-cell dysfunction and death and favors the development of diabetes. In this study, we demonstrate that HDLs protect β-cells against ER stress induced by thapsigargin, cyclopiazonic acid, palmitate, insulin overexpression, and high glucose concentrations. ER stress marker induction and ER morphology disruption mediated by these stimuli were inhibited by HDLs. Using a temperature-sensitive viral glycoprotein folding mutant, we show that HDLs correct impaired protein trafficking and folding induced by thapsigargin and palmitate. The ability of HDLs to protect β-cells against ER stress was inhibited by brefeldin A, an ER to Golgi trafficking blocker. These results indicate that HDLs restore ER homeostasis in response to ER stress, which is required for their ability to promote β-cell survival. This study identifies a cellular mechanism mediating the beneficial effect of HDLs on β-cells against ER stress-inducing factors.
- Published
- 2012