PMID- 23828564
OWN - NLM
STAT- MEDLINE
DCOM- 20140225
LR  - 20220317
IS  - 2041-4889 (Electronic)
VI  - 4
IP  - 7
DP  - 2013 Jul 4
TI  - Endoplasmic reticulum stress sensitizes pancreatic beta cells to 
      interleukin-1beta-induced apoptosis via Bim/A1 imbalance.
PG  - e701
LID - 10.1038/cddis.2013.236 [doi]
AB  - We have recently shown that the crosstalk between mild endoplasmic reticulum (ER) 
      stress and low concentrations of the pro-inflammatory cytokine interleukin 
      (IL)-1beta exacerbates beta cell inflammatory responses via the IRE1alpha/XBP1 pathway. 
      We presently investigated whether mild ER stress also sensitizes beta cells to 
      cytokine-induced apoptosis. Cyclopiazonic acid (CPA)-induced ER stress enhanced 
      the IL-1beta apoptosis in INS-1E and primary rat beta cells. This was not prevented 
      by XBP1 knockdown (KD), indicating the dissociation between the pathways leading 
      to inflammation and cell death. Analysis of the role of pro- and anti-apoptotic 
      proteins in cytokine-induced apoptosis indicated a central role for the 
      pro-apoptotic BH3 (Bcl-2 homology 3)-only protein Bim (Bcl-2-interacting mediator 
      of cell death), which was counteracted by four anti-apoptotic Bcl-2 (B-cell 
      lymphoma-2) proteins, namely Bcl-2, Bcl-XL, Mcl-1 and A1. CPA+IL-1beta-induced beta 
      cell apoptosis was accompanied by increased expression of Bim, particularly the 
      most pro-apoptotic variant, small isoform of Bim (BimS), and decreased expression 
      of A1. Bim silencing protected against CPA+IL-1beta-induced apoptosis, whereas A1 KD 
      aggravated cell death. Bim inhibition protected against cell death caused by A1 
      silencing under all conditions studied. In conclusion, mild ER stress predisposes 
      beta cells to the pro-apoptotic effects of IL-1beta by disrupting the balance 
      between pro- and anti-apoptotic Bcl-2 proteins. These findings link ER stress to 
      exacerbated apoptosis during islet inflammation and provide potential mechanistic 
      targets for beta cell protection, namely downregulation of Bim and upregulation 
      of A1.
FAU - Miani, M
AU  - Miani M
AD  - Laboratory of Experimental Medicine, Universite Libre de Bruxelles (ULB), 
      Brussels, Belgium.
FAU - Barthson, J
AU  - Barthson J
FAU - Colli, M L
AU  - Colli ML
FAU - Brozzi, F
AU  - Brozzi F
FAU - Cnop, M
AU  - Cnop M
FAU - Eizirik, D L
AU  - Eizirik DL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130704
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BCL2-related protein A1)
RN  - 0 (Bcl-2-Like Protein 11)
RN  - 0 (Bcl2l11 protein, rat)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Indoles)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Mcl1 protein, rat)
RN  - 0 (Membrane Proteins)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Myeloid Cell Leukemia Sequence 1 Protein)
RN  - 0 (Protein Isoforms)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Regulatory Factor X Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (X-Box Binding Protein 1)
RN  - 0 (Xbp1 protein, rat)
RN  - X9TLY4580Z (cyclopiazonic acid)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Apoptosis Regulatory Proteins/*metabolism
MH  - Bcl-2-Like Protein 11
MH  - Cell Line
MH  - DNA-Binding Proteins/metabolism
MH  - *Endoplasmic Reticulum Stress
MH  - Indoles
MH  - Insulin-Secreting Cells/*physiology
MH  - Interleukin-1beta/*physiology
MH  - Membrane Proteins/*metabolism
MH  - Minor Histocompatibility Antigens
MH  - Myeloid Cell Leukemia Sequence 1 Protein/metabolism
MH  - Protein Isoforms
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/*metabolism
MH  - Rats
MH  - Regulatory Factor X Transcription Factors
MH  - Transcription Factors/metabolism
MH  - X-Box Binding Protein 1
PMC - PMC3730410
EDAT- 2013/07/06 06:00
MHDA- 2014/02/26 06:00
PMCR- 2013/07/01
CRDT- 2013/07/06 06:00
PHST- 2013/03/12 00:00 [received]
PHST- 2013/05/10 00:00 [revised]
PHST- 2013/05/29 00:00 [accepted]
PHST- 2013/07/06 06:00 [entrez]
PHST- 2013/07/06 06:00 [pubmed]
PHST- 2014/02/26 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - cddis2013236 [pii]
AID - 10.1038/cddis.2013.236 [doi]
PST - epublish
SO  - Cell Death Dis. 2013 Jul 4;4(7):e701. doi: 10.1038/cddis.2013.236.