Novel Insights into the Global Proteome Responses of Insulin-Producing INS-1E Cells To Different Degrees of Endoplasmic Reticulum Stress

W. D'Hertog, M. Maris, G.B. Ferreira, E. Verdrengh, K. Lage, Daniel Aaen Hansen, A.K. Cardozo, Christopher Workman, Y. Moreau, D.L. Eizirik, E. Waelkens, L. Overbergh, C. Mathieu

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Exposure of insulin-secreting beta-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, beta-cell dysfunction, and eventually apoptotic beta-cell death. The aim of this study was to investigate the impact of ER stress on beta-cells at the protein level to evaluate the contribution of post-transcriptional and post-translational changes in ER stress-induced beta-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 mu M, led to massive apoptosis, accompanied by a near complete protein translation shut-down. CPA, 6.25 mu M, led to adaptation of the beta-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 beta-cell dysfunction and death.
    Original languageEnglish
    JournalJournal of Proteome Research
    Volume9
    Issue number10
    Pages (from-to)5142-5152
    ISSN1535-3893
    DOIs
    Publication statusPublished - 2010

    Keywords

    • Type 1 diabetes
    • 2D-DIGE
    • endoplasmic reticulum stress
    • INS-1E

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