Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells.
Cell Physiol Biochem
; 51(5): 2185-2197, 2018.
Article
em En
| MEDLINE
| ID: mdl-30537728
ABSTRACT
BACKGROUND/AIMS:
VCP-interacting membrane selenoprotein (VIMP), an ER resident selenoprotein, is highly expressed in ß-cells, however, the role of VIMP in ß-cells has not been characterized. In this study, we studied the relationship between VIMP deficiency and ß-cell survival in MIN6 insulinoma cells.METHODS:
To determine the role of VIMP in ß-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 ß-cell apoptosis, which is associated with a decrease in Bcl-xL, and the ß-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 IRE1α and PERK pathways; 4) VIMP KD increases insulin secretion.CONCLUSION:
These results suggest that VIMP may function as a novel regulator to modulate ß-cell survival, proliferation, cell cycle, UPR and insulin secretion in MIN6 cells.Palavras-chave
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Assunto principal:
Neoplasias Pancreáticas
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Regulação para Baixo
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Regulação Neoplásica da Expressão Gênica
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Células Secretoras de Insulina
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Selenoproteínas
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Pontos de Checagem da Fase G1 do Ciclo Celular
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Insulinoma
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Proteínas de Membrana
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article