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, FMM
dc.creatorFerreira, SM
dc.creatorBoschero, AC
dc.creatorSouza, KLA
dc.date2013
dc.date42186
dc.date2014-07-30T14:03:33Z
dc.date2015-11-26T17:39:43Z
dc.date2014-07-30T14:03:33Z
dc.date2015-11-26T17:39:43Z
dc.date.accessioned2018-03-29T00:21:17Z
dc.date.available2018-03-29T00:21:17Z
dc.identifierMolecular And Cellular Endocrinology. Elsevier Ireland Ltd, v. 374, n. 41671, n. 56, n. 64, 2013.
dc.identifier0303-7207
dc.identifierWOS:000321170000006
dc.identifier10.1016/j.mce.2013.04.009
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/57700
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/57700
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1286518
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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-1 beta. 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 IFNgamma 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. (c) 2013 Elsevier Ireland Ltd. All rights reserved.
dc.description374
dc.description41671
dc.description56
dc.description64
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageen
dc.publisherElsevier Ireland Ltd
dc.publisherClare
dc.publisherIrlanda
dc.relationMolecular And Cellular Endocrinology
dc.relationMol. Cell. Endocrinol.
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectHydrogen peroxide
dc.subjectDiabetes
dc.subjectGene expression regulation
dc.subjectPRX6
dc.subjectProteolysis
dc.subjectROS
dc.subjectNf-kappa-b
dc.subjectSignaling Pathway
dc.subjectNitric-oxide
dc.subjectExpression
dc.subjectApoptosis
dc.subjectInterleukin-1-beta
dc.subjectActivation
dc.subjectMechanism
dc.subjectCalpain
dc.subjectIslets
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


Este ítem pertenece a la siguiente institución