Title: Novel Insights into the Global Proteome Responses of Insulin-Producing INS-1E Cells To Different Degrees of Endoplasmic Reticulum Stress
Authors: D'Hertog, Wannes
Maris, Michael
Ferreira, Gabriela B
Verdrengh, Eefje
Lage, Kasper
Hansen, Daniel A
Cardozo, Alessandra K
Workman, Christopher T
Moreau, Yves
Eizirik, Decio L
Waelkens, Etienne
Overbergh, Lutgart ×
Mathieu, Chantal #
Issue Date: Oct-2010
Publisher: American Chemical Society
Series Title: Journal of Proteome Research vol:9 issue:10 pages:5142-5152
Abstract: Exposure of insulin-secreting β-cells to inflammatory cytokines or high concentrations of free fatty acids, factors involved in the pathogenesis of type 1 and type 2 diabetes, leads to endoplasmic reticulum (ER) stress, β-cell dysfunction, and eventually apoptotic β-cell death. The aim of this study was to investigate the impact of ER stress on β-cells at the protein level to evaluate the contribution of post-transcriptional and post-translational changes in ER stress-induced β-cell damage. INS-1E cells were exposed in vitro to the ER-stress inducer cyclopiazonic acid (CPA) at two concentrations, and protein changes were evaluated using 2D-DIGE. CPA, 25 μM, led to massive apoptosis, accompanied by a near complete protein translation shut-down. CPA, 6.25 μM, led to adaptation of the β-cells to ER stress. Identification of the differentially expressed proteins in the two conditions led to the discovery of a clear pattern of defense pathways, with post-translational modifications playing a crucial role. Key alterations included inhibition of insulin translation and post-translational modifications in ER chaperones HYOU1 and HSPA5. Also, a central role for 14-3-3 proteins is suggested. In conclusion, INS-1E cells are highly sensitive to ER stress, leading to important post-transcriptional and post-translational modifications that may contribute to β-cell dysfunction and death.
ISSN: 1535-3893
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Microbial and Molecular Systems - miscellaneous
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Molecular Virology and Gene Therapy
Laboratory of Protein Phosphorylation and Proteomics
Laboratory of Phosphoproteomics (-)
× corresponding author
# (joint) last author

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