Novel Insights into the Global Proteome Responses of Insulin-Producing INS-1E Cells To Different Degrees of Endoplasmic Reticulum Stress
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- 作者：Wannes D’ ; Hertog ; Michael Maris ; Gabriela B. Ferreira ; Eefje Verdrengh ; Kasper Lage ; Daniel A. Hansen ; Alessandra K. Cardozo ; Christopher T. Workman ; Yves Moreau ; Decio L. Eizirik ; Etienne Waelke
- 刊名：Journal of Proteome Research
- 出版年：2010
- 出版时间：October 1, 2010
- 年：2010
- 卷：9
- 期：10
- 页码：5142-5152
- 全文大小：556K
- 年卷期：v.9,no.10(October 1, 2010)
- ISSN：1535-3907
文摘
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.