CXC Chemokine Ligand 12 Protects Pancreatic β-Cells from Necrosis through Akt Kinase-Mediated Modulation of Poly(ADP-ribose) Polymerase-1 Activity
2014
Аутори:
Grdović, NevenaDinić, Svetlana
Mihailović, Mirjana
Uskoković, Aleksandra
Arambašić Jovanović, Jelena
Poznanović, Goran
Wagner, Ludwig
Vidaković, Melita
Cohen-Armon, Malka
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
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.
Извор:
PLOS One, 2014, 9, 7, e101172-Финансирање / пројекти:
- Сигнални молекули у дијабетесу: идентификација потенцијалних биолошких маркера укључених у модификацију и интеграцију сигналних путева у циљу предикције и интервенције у дијабетесу (RS-MESTD-Basic Research (BR or ON)-173020)
DOI: 10.1371/journal.pone.0101172
ISSN: 1932-6203
PubMed: 24988468
WoS: 000341354100067
Scopus: 2-s2.0-84903760208
URI
http://dx.plos.org/10.1371/journal.pone.0101172https://radar.ibiss.bg.ac.rs/handle/123456789/3184