Abstract
The diabetes prevention paradigm envisages the application of strategies that support the maintenance of appropriate β-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 β-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 β-cell viability which is based on its antinecrotic action through modulation of PARP-1 activity.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Line, Tumor
-
Chemokine CXCL12 / genetics
-
Chemokine CXCL12 / metabolism*
-
Hydrogen Peroxide / adverse effects
-
Hydrogen Peroxide / pharmacology
-
Insulin-Secreting Cells / metabolism*
-
Insulin-Secreting Cells / pathology
-
Male
-
Necrosis
-
Oxidants / adverse effects
-
Oxidants / pharmacology
-
Poly (ADP-Ribose) Polymerase-1
-
Poly(ADP-ribose) Polymerases / genetics
-
Poly(ADP-ribose) Polymerases / metabolism*
-
Protein Processing, Post-Translational*
-
Proto-Oncogene Proteins c-akt / genetics
-
Proto-Oncogene Proteins c-akt / metabolism*
-
Rats
-
Rats, Wistar
-
Signal Transduction / drug effects
-
Signal Transduction / genetics
Substances
-
CXCL12 protein, rat
-
Chemokine CXCL12
-
Oxidants
-
Hydrogen Peroxide
-
Parp1 protein, rat
-
Poly (ADP-Ribose) Polymerase-1
-
Poly(ADP-ribose) Polymerases
-
Proto-Oncogene Proteins c-akt
Grants and funding
This work was financed by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant No. 173020). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.