Modulation Of The Peroxiredoxin System By Cytokines In Insulin-producing Rinm5f Cells: Down-regulation Of Prdx6 Increases Susceptibility Of Beta Cells To Oxidative Stress.

dc.creatorPaula, Flavia M M
dc.creatorFerreira, Sandra M
dc.creatorBoschero, Antonio C
dc.creatorSouza, Kleber L A
dc.date2013-Jul
dc.date2015-11-27T13:31:40Z
dc.date2015-11-27T13:31:40Z
dc.date.accessioned2018-03-29T01:17:41Z
dc.date.available2018-03-29T01:17:41Z
dc.identifierMolecular And Cellular Endocrinology. v. 374, n. 1-2, p. 56-64, 2013-Jul.
dc.identifier1872-8057
dc.identifier10.1016/j.mce.2013.04.009
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/23623867
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/200608
dc.identifier23623867
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1300841
dc.descriptionPeroxiredoxins 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.
dc.description374
dc.description56-64
dc.languageeng
dc.relationMolecular And Cellular Endocrinology
dc.relationMol. Cell. Endocrinol.
dc.rightsfechado
dc.rightsCopyright © 2013 Elsevier Ireland Ltd. All rights reserved.
dc.sourcePubMed
dc.subjectAnimals
dc.subjectCalpain
dc.subjectCell Line
dc.subjectGene Expression Regulation
dc.subjectInsulin
dc.subjectInsulin-secreting Cells
dc.subjectInterferon-gamma
dc.subjectInterleukin-1beta
dc.subjectInterleukin-4
dc.subjectMap Kinase Kinase 4
dc.subjectOxidative Stress
dc.subjectPeroxiredoxin Vi
dc.subjectProteasome Endopeptidase Complex
dc.subjectProteolysis
dc.subjectRna, Messenger
dc.subjectRats
dc.subjectSignal Transduction
dc.subjectTumor Necrosis Factor-alpha
dc.titleModulation Of The Peroxiredoxin System By Cytokines In Insulin-producing Rinm5f Cells: Down-regulation Of Prdx6 Increases Susceptibility Of Beta Cells To Oxidative Stress.
dc.typeArtículos de revistas


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