Subtle shifts in the ratio between pro- and antiapoptotic molecules after activation of corticosteroid receptors decide neuronal fate

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dc.contributor.authorAlmeida, O. F. X.en
dc.contributor.authorConde, G. L.en
dc.contributor.authorCrochemore, C.en
dc.contributor.authorDemeneix, B. A.en
dc.contributor.authorFischer, D.en
dc.contributor.authorHassan, A. H. S.en
dc.contributor.authorMeyer, M.en
dc.contributor.authorHolsboer, F.en
dc.contributor.authorMichaelidis, T. M.en
dc.date.accessioned2015-11-24T16:32:19Z
dc.date.available2015-11-24T16:32:19Z
dc.identifier.issn0892-6638-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/7541
dc.rightsDefault Licence-
dc.subjectapoptosisen
dc.subjectbcl-2en
dc.subjectbaxen
dc.subjectbax knockout mouseen
dc.subjectcorticosteroneen
dc.subjectdexamethasoneen
dc.subjectmineralocorticoid receptoren
dc.subjectglucocorticoid receptoren
dc.subjectsteroid-hormone receptorsen
dc.subjectprogrammed cell-deathen
dc.subjecttumor-suppressor p53en
dc.subjectbcl-2 gene familyen
dc.subjectdentate gyrusen
dc.subjectin-vivoen
dc.subjectglucocorticen
dc.titleSubtle shifts in the ratio between pro- and antiapoptotic molecules after activation of corticosteroid receptors decide neuronal fateen
heal.abstractGlucocorticoid receptor (GR) activation induces apoptosis of granule cells in the hippocampus. In contrast, neuroprotection is seen after mineralocorticoid receptor (MR) activation. To date there is no in vivo evidence for direct interactions between corticosteroids and any of the key regulatory molecules of programmed cell death. In this report, we show that the opposing actions of MR and GR on neuronal survival result from their ability to differentially influence the expression of members of the bcl-2 gene family; specifically; in the rat hippocampus, activation of GR induces cell death by increasing the ratio of the proapoptotic molecule Bax relative to the antiapoptotic molecules Bcl-2 or Bcl-x(L); the opposite effect is oh served after stimulation of MR. The same results were obtained in both young and aged animals; however, older subjects (which were more susceptible to GR-mediated apoptosis) tended to express the antiapoptotic genes more robustly. Using a loss-of-function mouse model, we corroborated the observations made in the rat, demonstrating Bax to be essential in the GR-mediated cell death-signaling cascade. In addition, we show that GR activation increases and MR activation decreases levels of the tumor suppressor protein p53 (a direct transcriptional regulator of bax and bcl-2 genes), thus providing new information on the early genetic events linking corticosteroid receptors with apoptosis in the nervous system.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondary<Go to ISI>://000086292700015-
heal.identifier.secondaryhttp://www.fasebj.org/content/14/5/779.full.pdf-
heal.journalNameFaseb Journalen
heal.journalTypepeer reviewed-
heal.languageen-
heal.publicationDate2000-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιώνel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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