PMID- 19085810
OWN - NLM
STAT- MEDLINE
DCOM- 20090521
LR  - 20181201
IS  - 1439-4286 (Electronic)
IS  - 0018-5043 (Linking)
VI  - 41
IP  - 4
DP  - 2009 Apr
TI  - Anti-apoptotic action of exendin-4 in INS-1 beta cells: comparative protein 
      pattern analysis of isolated mitochondria.
PG  - 294-301
LID - 10.1055/s-0028-1105911 [doi]
AB  - Glucagon like peptide-1 (Glp-1) exhibits beneficial effects on beta cell mass by 
      both enhancing proliferation and inhibiting apoptosis. The precise mechanism of 
      the anti-apoptotic effect of Glp-1 and Glp-1 mimetics like exendin-4 has remained 
      elusive. Here, we studied cytokine-induced apoptosis in the pancreatic beta cell 
      line INS-1 and performed a comparative mitochondrial protein pattern analysis 
      using two-dimensional difference gel electrophoresis (2D-DIGE). Cytokine 
      incubation of INS-1 cells increased caspase-3 activity about 3-fold, which was 
      reduced by 60% in the presence of exendin-4. Production of reactive oxygen 
      species in response to cytokines was completely prevented after preincubation 
      with exendin-4. Highly purified mitochondria were obtained and mitochondrial 
      proteins were labeled with Cy-dyes and separated on overlapping zoom 2D gels 
      spanning a pH-range of 4-9. Protein spots with significant changes after cytokine 
      and exendin-4 treatment were identified by MALDI mass spectrometry. Comparing all 
      treatment conditions, comparative mitochondrial proteome analysis allowed to 
      identify 33 different proteins, which were significantly altered between 
      comparison groups. Changes in protein patterns revealed involvement of 
      cytokine-induced electron transport chain damage. Thus, cytochrome bc1 complex 
      subunit I and ATP synthase subunit beta were downregulated by 30-40%. This was 
      abrogated by the presence of exendin-4. In conclusion, this study provides 
      further insights into the role of mitochondria in cytokine-induced apoptosis. We 
      show here that exendin-4 significantly counter-regulates the reduced abundance of 
      electron transport chain proteins, leading to a reduction of oxidative stress and 
      most likely contributing to the anti-apoptotic action of this drug.
FAU - Tews, D
AU  - Tews D
AD  - Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, 
      Dusseldorf, Germany.
FAU - Lehr, S
AU  - Lehr S
FAU - Hartwig, S
AU  - Hartwig S
FAU - Osmers, A
AU  - Osmers A
FAU - Paslack, W
AU  - Paslack W
FAU - Eckel, J
AU  - Eckel J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081215
PL  - Germany
TA  - Horm Metab Res
JT  - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et 
      metabolisme
JID - 0177722
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Peptides)
RN  - 0 (Venoms)
RN  - 9P1872D4OL (Exenatide)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Exenatide
MH  - Insulin-Secreting Cells/chemistry/*cytology/drug effects
MH  - Mitochondria/chemistry/drug effects/*metabolism
MH  - Mitochondrial Proteins/chemistry/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Peptides/*pharmacology
MH  - Venoms/*pharmacology
EDAT- 2008/12/17 09:00
MHDA- 2009/05/22 09:00
CRDT- 2008/12/17 09:00
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/05/22 09:00 [medline]
AID - 10.1055/s-0028-1105911 [doi]
PST - ppublish
SO  - Horm Metab Res. 2009 Apr;41(4):294-301. doi: 10.1055/s-0028-1105911. Epub 2008 
      Dec 15.