PMID- 20933054
OWN - NLM
STAT- MEDLINE
DCOM- 20110429
LR  - 20161125
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 332
IP  - 1-2
DP  - 2011 Jan 30
TI  - Modulation of Bcl-2-related protein expression in pancreatic beta cells by 
      pro-inflammatory cytokines and its dependence on the antioxidative defense 
      status.
PG  - 88-96
LID - 10.1016/j.mce.2010.09.017 [doi]
AB  - Pro-inflammatory cytokines are key mediators in the selective and progressive 
      destruction of insulin-producing beta cells during type 1 diabetes development. 
      However, the mechanisms of cytokine-induced beta cell apoptosis are not fully 
      understood. This study demonstrates that pro-inflammatory cytokines strongly 
      modified the expression of the anti-apoptotic protein Bcl-2 and the pro-apoptotic 
      BH3-only proteins Bad, Bim, and Bid in primary rat islets and insulin-producing 
      RINm5F cells. Overexpression of mitochondrially located catalase (MitoCatalase) 
      specifically increased basal Bcl-2 and decreased basal Bax expression, suppressed 
      cytokine-mediated reduction of Bcl-2, and thereby prevented the release of 
      cytochrome c, Smac/DIABLO and the activation of caspase-9 and -3. Thus, 
      cytokine-mediated decrease of Bcl-2 expression and the sequentially changed 
      Bax/Bcl-2 ratio are responsible for the release of pro-apoptotic mitochondrial 
      factors, activation of caspase-9, and ultimately caspase-3. These results 
      indicate that activation of the intrinsic/mitochondrial apoptosis pathway is 
      essential for cytokine-induced beta cell death and the mitochondrial generation 
      of reactive oxygen species, in particular mitochondrial hydrogen peroxide, 
      differentially regulates the Bax/Bcl-2 ratio.
CI  - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Mehmeti, Ilir
AU  - Mehmeti I
AD  - Institute of Clinical Biochemistry, Hannover Medical School, 30623 Hannover, 
      Germany.
FAU - Lenzen, Sigurd
AU  - Lenzen S
FAU - Lortz, Stephan
AU  - Lortz S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101007
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Antioxidants)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BH3 Interacting Domain Death Agonist Protein)
RN  - 0 (Bcl-2-Like Protein 11)
RN  - 0 (Bcl2l11 protein, rat)
RN  - 0 (Cytokines)
RN  - 0 (Membrane Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - Apoptosis/physiology
MH  - Apoptosis Regulatory Proteins/genetics/metabolism
MH  - BH3 Interacting Domain Death Agonist Protein/genetics/metabolism
MH  - Bcl-2-Like Protein 11
MH  - Caspase 3/metabolism
MH  - Caspase 9/metabolism
MH  - Catalase/genetics/metabolism
MH  - Cell Line
MH  - Cytokines/*metabolism
MH  - Insulin-Secreting Cells/cytology/*metabolism
MH  - Male
MH  - Membrane Proteins/genetics/metabolism
MH  - Mitochondria/metabolism
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Reactive Oxygen Species/metabolism
MH  - bcl-2-Associated X Protein/genetics/metabolism
EDAT- 2010/10/12 06:00
MHDA- 2011/04/30 06:00
CRDT- 2010/10/12 06:00
PHST- 2010/05/03 00:00 [received]
PHST- 2010/09/03 00:00 [revised]
PHST- 2010/09/28 00:00 [accepted]
PHST- 2010/10/12 06:00 [entrez]
PHST- 2010/10/12 06:00 [pubmed]
PHST- 2011/04/30 06:00 [medline]
AID - S0303-7207(10)00488-0 [pii]
AID - 10.1016/j.mce.2010.09.017 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2011 Jan 30;332(1-2):88-96. doi: 10.1016/j.mce.2010.09.017. 
      Epub 2010 Oct 7.