Protection of insulin-producing cells against toxicity of dexamethasone by catalase overexpression

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dc.contributor.authorRoma, Leticia P.
dc.contributor.authorBosqueiro, José Roberto [UNESP]
dc.contributor.authorCunha, Daniel A.
dc.contributor.authorCarneiro, Everardo M.
dc.contributor.authorGurgul-Convey, Ewa
dc.contributor.authorLenzen, Sigurd
dc.contributor.authorBoschero, Antonio C.
dc.contributor.authorSouza, Kleber L. A.
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionHannover Med Sch
dc.date.accessioned2014-05-20T13:26:06Z
dc.date.available2014-05-20T13:26:06Z
dc.date.issued2009-11-15
dc.description.abstractPancreatic cells are very sensitive to reactive oxygen species (ROS) and this might play an important role in beta cell death in diabetes. Dexamethasone is a synthetic diabetogenic glucocorticoid, which impairs pancreatic beta cell function. Therefore we investigated the toxicity of dexamethasone in RINm5F insulin-producing cells and its dependence on the expression level of the antioxidant enzyme catalase, which inactivates hydrogen peroxide. This was correlated with oxidative stress and cell death. An increased generation of ROS was observed in dexamethasone-treated cells together with an increase in caspase-3 activity and apoptosis rate. Interestingly, exposure to dexamethasone increased the cytosolic superoxide dismutase Cu/ZnSOD protein expression and activity, whereas the mitochondrial MnSOD isoform was not affected by the glucocorticoid. Catalase overexpression in insulin-producing cells prevented all the cytotoxic effects of dexamethasone. In conclusion, dexamethasone-induced cell death in insulin-producing cells is ROS mediated. Increased levels of expression and activity of the Cu/ZnSOD might favor the generation of hydrogen peroxide in dexamethasone-treated cells. Increased ROS scavenging capacity in insulin-producing cells, through overexpression of catalase, prevents a deleterious increase in hydrogen peroxide generation and thus prevents dexamethasone-induced apoptosis. (C) 2009 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Estadual Campinas, Inst Biol, Dept Physiol & Biophys, BR-13083970 Campinas, SP, Brazil
dc.description.affiliationSão Paulo State Univ, Dept Phys Educ, Bauru, SP, Brazil
dc.description.affiliationHannover Med Sch, Inst Clin Biochem, D-3000 Hannover, Germany
dc.description.affiliationUnespSão Paulo State Univ, Dept Phys Educ, Bauru, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipEuropean Union
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdEU: LSHM-CT-2006-518153
dc.description.sponsorshipIdEU: LSHM-CT-2006-036903
dc.format.extent1386-1393
dc.identifierhttp://dx.doi.org/10.1016/j.freeradbiomed.2009.08.010
dc.identifier.citationFree Radical Biology and Medicine. New York: Elsevier B.V., v. 47, n. 10, p. 1386-1393, 2009.
dc.identifier.doi10.1016/j.freeradbiomed.2009.08.010
dc.identifier.issn0891-5849
dc.identifier.lattes2423477869556138
dc.identifier.urihttp://hdl.handle.net/11449/8361
dc.identifier.wosWOS:000271934400008
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofFree Radical Biology and Medicine
dc.relation.ispartofjcr6.020
dc.relation.ispartofsjr2,178
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectOxidative stressen
dc.subjectGlucocorticoidsen
dc.subjectCaspasesen
dc.subjectNecrosisen
dc.subjectInsulin-secreting cellsen
dc.subjectIslets of Langerhansen
dc.subjectDrug effectsen
dc.subjectPharmacologyen
dc.subjectIn vitroen
dc.subjectFree radicalsen
dc.subjectHyperProteinen
dc.subjectHyPer Vectoren
dc.titleProtection of insulin-producing cells against toxicity of dexamethasone by catalase overexpressionen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderElsevier B.V.
unesp.author.lattes2423477869556138
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências, Baurupt
unesp.departmentEducação Física - FCpt

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