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Type: Artigo de periódico
Title: Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis
Author: Rezende, LF
Vieira, AS
Negro, A
Langone, F
Boschero, AC
Abstract: CNTF is a cytokine that promotes survival and/or differentiation in many cell types, including rat pancreatic islets. In this work, we studied the mechanism of CNTF signal in neonatal rats pancreatic islets isolated by the collagenase method and cultured for 3 days in RPMI medium without (CTL) or with 1 nM of CNTF. The medium contained, when necessary, specific inhibitors of the PI3K, MAPK and JAK/STAT3 pathways. mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of Akt, ERK1/2 and STAT3, and SOCS-3 (RT-PCR and Western blot), as well as glucose-stimulated insulin secretion (GSIS) (Radioimmunoassay), were analyzed. Our results showed that Akt, ERK1 and STAT3 mRNA expression, as well as phosphorylated Akt and ERK1/2, was not affected by CNTF treatment. CNTF increased cytoplasmatic and nuclear phosphorylated STAT3, and the SOCS3 mRNA and protein expression. In addition, CNTF lowered apoptosis and impaired GSIS. These effects were blocked by the JAK inhibitor, AG490 and by the STAT inhibitor Curcumin, but not by the MAPK inhibitor, PD98059, nor by the PI3K inhibitor, Wortmannin. In conclusion, CNTF signals through the JAK2/STAT3 cascade, increases SOCS3 expression, impairs GSIS and protects neonatal pancreatic rat islets from cytokine-induced apoptosis. These findings indicate that CNTF may be a potential therapeutic tool against Type 1 and/or Type 2 diabetes. (C) 2009 Elsevier Ltd. All rights reserved.
Subject: STAT3
Pancreatic islets
Country: Inglaterra
Editor: Academic Press Ltd- Elsevier Science Ltd
Citation: Cytokine. Academic Press Ltd- Elsevier Science Ltd, v. 46, n. 1, n. 65, n. 71, 2009.
Rights: fechado
Identifier DOI: 10.1016/j.cyto.2008.12.014
Date Issue: 2009
Appears in Collections:Unicamp - Artigos e Outros Documentos

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