HDLs protect the MIN6 insulinoma cell line against tunicamycin-induced apoptosis without inhibiting ER stress and without restoring ER functionality

Autor: Julien Puyal, Christian Widmann, Coralie Rummel, Jannick Pétremand, Gilles Dubuis
Rok vydání: 2013
Předmět:
Endoplasmic Reticulum/ultrastructure
Apoptosis
Endoplasmic Reticulum
Biochemistry
Transcription Factor CHOP/metabolism
Mice
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Extracellular Signal-Regulated MAP Kinases/metabolism
Insulin-Secreting Cells
Endoplasmic Reticulum/physiology
Proto-Oncogene Proteins c-akt/metabolism
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
0303 health sciences
DNA-Binding Proteins/metabolism
Chemistry
Tunicamycin
Endoplasmic Reticulum Stress
Cell biology
DNA-Binding Proteins
Insulin-Secreting Cells/drug effects
Thapsigargin
Lipoproteins
HDL
Insulin-Secreting Cells/physiology
medicine.medical_specialty
Glycosylation
MAP Kinase Signaling System
Tunicamycin/pharmacology
Regulatory Factor X Transcription Factors
030209 endocrinology & metabolism
Lipoproteins
HDL/physiology
03 medical and health sciences
Cell Line
Tumor
Internal medicine
medicine
Animals
Humans
Transcription Factors/metabolism
Thapsigargin/pharmacology
Molecular Biology
Insulinoma
030304 developmental biology
JNK Mitogen-Activated Protein Kinases/metabolism
Endoplasmic reticulum
Apoptosis/drug effects
Heat-Shock Proteins/metabolism
JNK Mitogen-Activated Protein Kinases
medicine.disease
HEK293 Cells
Cytoprotection
Cell culture
Unfolded protein response
Protein Processing
Post-Translational
Proto-Oncogene Proteins c-akt
Transcription Factor CHOP
Transcription Factors
Zdroj: Molecular and Cellular Endocrinology, vol. 381, no. 1-2, pp. 291-301
Molecular and Cellular Endocrinology
ISSN: 0303-7207
DOI: 10.1016/j.mce.2013.08.016
Popis: HDLs protect pancreatic beta cells against apoptosis induced by several endoplasmic reticulum (ER) stressors, including thapsigargin, cyclopiazonic acid, palmitate and insulin over-expression. This protection is mediated by the capacity of HDLs to maintain proper ER morphology and ER functions such as protein folding and trafficking. Here, we identified a distinct mode of protection exerted by HDLs in beta cells challenged with tunicamycin (TM), a protein glycosylation inhibitor inducing ER stress. HDLs were found to inhibit apoptosis induced by TM in the MIN6 insulinoma cell line and this correlated with the maintenance of a normal ER morphology. Surprisingly however, this protective response was neither associated with a significant ER stress reduction, nor with restoration of protein folding and trafficking in the ER. These data indicate that HDLs can use at least two mechanisms to protect beta cells against ER stressors. One that relies on the maintenance of ER function and one that operates independently of ER function modulation. The capacity of HDLs to activate several anti-apoptotic pathways in beta cells may explain their ability to efficiently protect these cells against a variety of insults.
Databáze: OpenAIRE
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