PMID- 30537728
OWN - NLM
STAT- MEDLINE
DCOM- 20190125
LR  - 20191210
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 51
IP  - 5
DP  - 2018
TI  - Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell 
      Cycle Arrest and Cell Death in MIN6 Insulinoma Cells.
PG  - 2185-2197
LID - 10.1159/000495865 [doi]
AB  - 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 IRE1alpha 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.
CI  - (c) 2018 The Author(s). Published by S. Karger AG, Basel.
FAU - Men, Lili
AU  - Men L
AD  - Department of Endocrinology, First Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - Sun, Juan
AU  - Sun J
AD  - Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
FAU - Ren, Decheng
AU  - Ren D
AD  - Department of Medicine, The University of Chicago, Chicago, Illinois, 
      USArendckent@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20181207
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Membrane Proteins)
RN  - 0 (Selenoproteins)
RN  - 0 (Selenos protein, mouse)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Death
MH  - Cell Line, Tumor
MH  - *Down-Regulation
MH  - *G1 Phase Cell Cycle Checkpoints
MH  - *Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Insulin-Secreting Cells/metabolism/*pathology
MH  - Insulinoma/*genetics/pathology
MH  - Membrane Proteins/*genetics
MH  - Mice
MH  - Pancreatic Neoplasms/*genetics/pathology
MH  - Selenoproteins/*genetics
MH  - Unfolded Protein Response
OTO - NOTNLM
OT  - Cell cycle
OT  - Insulin secretion
OT  - MIN6 cells
OT  - UPR
OT  - beta-cell death
EDAT- 2018/12/12 06:00
MHDA- 2019/01/27 06:00
CRDT- 2018/12/12 06:00
PHST- 2017/10/09 00:00 [received]
PHST- 2018/11/29 00:00 [accepted]
PHST- 2018/12/12 06:00 [entrez]
PHST- 2018/12/12 06:00 [pubmed]
PHST- 2019/01/27 06:00 [medline]
AID - 000495865 [pii]
AID - 10.1159/000495865 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2018;51(5):2185-2197. doi: 10.1159/000495865. Epub 2018 Dec 
      7.