Progesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanism

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dc.contributor.authorNunes, V. A.
dc.contributor.authorPortioli-Sanches, E. P.
dc.contributor.authorRosim, M. P.
dc.contributor.authorAraujo, M. S. [UNIFESP]
dc.contributor.authorPraxedes-Garcia, P. [UNIFESP]
dc.contributor.authorValle, M. M. R.
dc.contributor.authorRoma, L. P.
dc.contributor.authorHahn, C.
dc.contributor.authorGurgul-Convey, E.
dc.contributor.authorLenzen, S.
dc.contributor.authorAzevedo-Martins, A. K.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionHannover Med Sch
dc.date.accessioned2016-01-24T14:37:10Z
dc.date.available2016-01-24T14:37:10Z
dc.date.issued2014-05-01
dc.description.abstractProgesterone has been associated with the development of gestational diabetes (GD) due to the enhancement of insulin resistance. As b-cell apoptosis participates in type 1 and type 2 diabetes pathophysiology, we proposed the hypothesis that progesterone might contribute to the development of GD through a mechanism that also involves b-cell death. To address this question, RINm5F insulin-producing cells were incubated with progesterone (25-100 mM), in the presence or absence of a-tocopherol (40 mM). After 24 or 48 h, membrane integrity andDNA fragmentation were analyzed by flow cytometry. Caspase activity was used to identify the mode of cell death. the involvement of endoplasmic reticulum stress in the action of progesterone was investigated by western blotting. Oxidative stress was measured by 2', 7'-dichlorofluorescein diacetate (DCFDA) oxidation. Isolated rat islets were used in similar experiments in order to confirm the effect of progesterone in primary b-cells. Incubation of RINm5F cells with progesterone increased the number of cells with loss of membrane integrity and DNA fragmentation. Progesterone induced generation of reactive species. Pre-incubation with a-tocopherol attenuated progesterone-induced apoptosis. Western blot analyses revealed increased expression of CREB2 and CHOP in progesteronetreated cells. Progesterone caused apoptotic death of rat islet cells and enhanced generation of reactive species. Our results show that progesterone can be toxic to pancreatic b-cells through an oxidative-stress-dependent mechanism that induces apoptosis. This effect may contribute to the development of GD during pregnancy, particularly under conditions that require administration of pharmacological doses of this hormone.en
dc.description.affiliationUniv São Paulo, Sch Arts Sci & Humanities, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Inst Biomed Sci, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biochem, São Paulo, Brazil
dc.description.affiliationHannover Med Sch, Inst Clin Biochem, Hannover, Germany
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biochem, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: 05607/2007
dc.format.extent273-284
dc.identifierhttp://dx.doi.org/10.1530/JOE-13-0202
dc.identifier.citationJournal of Endocrinology. Bristol: Bioscientifica Ltd, v. 221, n. 2, p. 273-284, 2014.
dc.identifier.doi10.1530/JOE-13-0202
dc.identifier.issn0022-0795
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/37696
dc.identifier.wosWOS:000337110900014
dc.language.isoeng
dc.publisherBioscientifica Ltd
dc.relation.ispartofJournal of Endocrinology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectinsulin-producing cellsen
dc.subjectprogesteroneen
dc.subjectoestriolen
dc.subjectapoptosisen
dc.subjectoxidative stressen
dc.subjectgestational diabetesen
dc.titleProgesterone induces apoptosis of insulin-secreting cells: insights into the molecular mechanismen
dc.typeinfo:eu-repo/semantics/article
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