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Type: Artigo de periódico
Title: Modulation Of The Peroxiredoxin System By Cytokines In Insulin-producing Rinm5f Cells: Down-regulation Of Prdx6 Increases Susceptibility Of Beta Cells To Oxidative Stress.
Author: Paula, Flavia M M
Ferreira, Sandra M
Boschero, Antonio C
Souza, Kleber L A
Abstract: Peroxiredoxins are a family of six antioxidant enzymes (PRDX1-6), and may be an alternative system for the pancreatic beta cells to cope with oxidative stress. This study investigated whether the main diabetogenic pro-inflammatory cytokines or the anti-inflammatory cytokine IL-4 modulate PRDXs levels and putative intracellular pathways important for this process in the insulin-producing RINm5F cells. RINm5F cells expressed significant amounts of PRDX1, PRDX3 and PRDX6 enzymes. Only PRDX6 was modulated by cytokines, showing both mRNA and protein down-regulation following incubation of RINm5F cells with TNF-alpha and IFN-gamma but not with IL-1beta. Separately IFN-gamma or TNF-alpha decreased PRDX6 protein but not mRNA levels. The blockage of the JNK signalling and of the calpains and proteasome proteolysis systems restored PRDX6 protein levels. IL-4 alone did not modulate PRDXs levels. However, pre/co-incubation with IL-4 substantially prevented the decrease in PRDX6 induced by pro-inflammatory cytokines. Knockdown of PRDX6 increased susceptibility of RINm5F cells to the deleterious effects of pro-inflammatory cytokines and to oxidative stress. These results show that, from the PRDXs significantly expressed in RINm5F cells, only PRDX6 is modulated by the diabetogenic cytokines IFN-gamma and TNF-alpha. This PRDX6 down-regulation depends on the calpain and proteasome systems and JNK signalling. PRDX6 is an important enzyme for protection against oxidative stress and the interaction between pro- and anti-inflammatory cytokines might be important to determine the antioxidant capacity of the cells.
Subject: Animals
Cell Line
Gene Expression Regulation
Insulin-secreting Cells
Map Kinase Kinase 4
Oxidative Stress
Peroxiredoxin Vi
Proteasome Endopeptidase Complex
Rna, Messenger
Signal Transduction
Tumor Necrosis Factor-alpha
Citation: Molecular And Cellular Endocrinology. v. 374, n. 1-2, p. 56-64, 2013-Jul.
Rights: fechado
Identifier DOI: 10.1016/j.mce.2013.04.009
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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