期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 51, 期 5, 页码 2185-2197出版社
KARGER
DOI: 10.1159/000495865
关键词
beta-cell death; UPR; Cell cycle; Insulin secretion; MIN6 cells
资金
- University of Chicago [P30-DK020595]
- Diabetes Research and Training Center [P30-DK020595]
Background/Aims: VCP-interacting membrane selenoprotein (VIMP), an ER resident selenoprotein, is highly expressed in beta-cells, however, the role of VIMP in beta-cells has not been characterized. In this study, we studied the relationship between VIMP deficiency and beta-cell survival in MIN6 insulinoma cells. Methods: To determine the role of VIMP in beta-cells, lentiviral VIMP shRNAs were used to knock down (KD) expression of VIMP in MIN6 cells. Cell death was quantified by propidium iodide (PI) staining followed by flow cytometric analyses using a FACS Caliber and FlowJo software. Cell apoptosis and proliferation were determined by TUNEL assay and Ki67 staining, respectively. Cell cycle was analyzed after PI staining. Results: The results show that 1) VIMP suppression induces beta-cell apoptosis, which is associated with a decrease in Bcl-xL, and the beta-cell apoptosis induced by VIMP suppression can be inhibited by overexpression of Bcl-xL; 2) VIMP knockdown (KD) decreases cell proliferation and G1 cell cycle arrest by accumulating p27 and decreasing E2F1; 3) VIMP KD suppresses unfolded protein response (UPR) activation by regulating the IRE1 alpha and PERK pathways; 4) VIMP KD increases insulin secretion. Conclusion: These results suggest that VIMP may function as a novel regulator to modulate beta-cell survival, proliferation, cell cycle, UPR and insulin secretion in MIN6 cells. (C) 2018 The Author(s) Published by S. Karger AG, Basel
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