PMID- 24988468
OWN - NLM
STAT- MEDLINE
DCOM- 20150221
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 7
DP  - 2014
TI  - CXC chemokine ligand 12 protects pancreatic beta-cells from necrosis through Akt 
      kinase-mediated modulation of poly(ADP-ribose) polymerase-1 activity.
PG  - e101172
LID - 10.1371/journal.pone.0101172 [doi]
LID - e101172
AB  - The diabetes prevention paradigm envisages the application of strategies that 
      support the maintenance of appropriate beta-cell numbers. Herein we show that 
      overexpression of CXC chemokine ligand12 (CXCL12) considerably improves the 
      viability of isolated rat Langerhans islet cells and Rin-5F pancreatic beta-cells 
      after hydrogen peroxide treatment. In rat islets and wt cells hydrogen peroxide 
      treatment induced necrotic cell death that was mediated by the rapid and 
      extensive activation of poly(ADP-ribose) polymerase-1 (PARP-1). In contrast, 
      CXCL12-overexpressing cells were protected from necrotic cell death as a result 
      of significantly reduced PARP-1 activity. CXCL12 downstream signalling through 
      Akt kinase was responsible for the reduction of PARP-1 activity which switched 
      cell death from necrosis to apoptosis, providing increased protection to cells 
      from oxidative stress. Our results offer a novel aspect of the CXCL12-mediated 
      improvement of beta-cell viability which is based on its antinecrotic action through 
      modulation of PARP-1 activity.
FAU - Grdovic, Nevena
AU  - Grdovic N
AD  - Department of Molecular Biology, Institute for Biological Research, University of 
      Belgrade, Belgrade, Serbia.
FAU - Dinic, Svetlana
AU  - Dinic S
AD  - Department of Molecular Biology, Institute for Biological Research, University of 
      Belgrade, Belgrade, Serbia.
FAU - Mihailovic, Mirjana
AU  - Mihailovic M
AD  - Department of Molecular Biology, Institute for Biological Research, University of 
      Belgrade, Belgrade, Serbia.
FAU - Uskokovic, Aleksandra
AU  - Uskokovic A
AD  - Department of Molecular Biology, Institute for Biological Research, University of 
      Belgrade, Belgrade, Serbia.
FAU - Jovanovic, Jelena Arambasic
AU  - Jovanovic JA
AD  - Department of Molecular Biology, Institute for Biological Research, University of 
      Belgrade, Belgrade, Serbia.
FAU - Poznanovic, Goran
AU  - Poznanovic G
AD  - Department of Molecular Biology, Institute for Biological Research, University of 
      Belgrade, Belgrade, Serbia.
FAU - Wagner, Ludwig
AU  - Wagner L
AD  - Department of Medicine III, Division of Nephrology and Dialysis, Medical 
      University of Vienna, Vienna, Austria.
FAU - Vidakovic, Melita
AU  - Vidakovic M
AD  - Department of Molecular Biology, Institute for Biological Research, University of 
      Belgrade, Belgrade, Serbia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140702
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CXCL12 protein, rat)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Oxidants)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.4.2.30 (Parp1 protein, rat)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Chemokine CXCL12/genetics/*metabolism
MH  - Hydrogen Peroxide/adverse effects/pharmacology
MH  - Insulin-Secreting Cells/*metabolism/pathology
MH  - Male
MH  - Necrosis
MH  - Oxidants/adverse effects/pharmacology
MH  - Poly (ADP-Ribose) Polymerase-1
MH  - Poly(ADP-ribose) Polymerases/genetics/*metabolism
MH  - *Protein Processing, Post-Translational
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects/genetics
PMC - PMC4079329
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/07/06 06:00
MHDA- 2015/02/24 06:00
PMCR- 2014/07/02
CRDT- 2014/07/03 06:00
PHST- 2014/04/08 00:00 [received]
PHST- 2014/06/03 00:00 [accepted]
PHST- 2014/07/03 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2015/02/24 06:00 [medline]
PHST- 2014/07/02 00:00 [pmc-release]
AID - PONE-D-14-15710 [pii]
AID - 10.1371/journal.pone.0101172 [doi]
PST - epublish
SO  - PLoS One. 2014 Jul 2;9(7):e101172. doi: 10.1371/journal.pone.0101172. eCollection 
      2014.