CXC chemokine ligand 12 protects pancreatic ß-cells from necrosis through Akt kinase-mediated modulation of poly(ADP-ribose) polymerase-1 activity.
PLoS One
; 9(7): e101172, 2014.
Article
em En
| MEDLINE
| ID: mdl-24988468
ABSTRACT
The diabetes prevention paradigm envisages the application of strategies that support the maintenance of appropriate ß-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 ß-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 ß-cell viability which is based on its antinecrotic action through modulation of PARP-1 activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Processamento de Proteína Pós-Traducional
/
Poli(ADP-Ribose) Polimerases
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Células Secretoras de Insulina
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Proteínas Proto-Oncogênicas c-akt
/
Quimiocina CXCL12
Limite:
Animals
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2014
Tipo de documento:
Article