Bcl-2 but not clusterin/apolipoprotein J protected human diploid fibroblasts and immortalized keratinocytes from ceramide-induced apoptosis: role of p53 in the ceramide response

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dc.contributor.authorKolettas, E.en
dc.contributor.authorSkoufos, I.en
dc.contributor.authorKontargiris, E.en
dc.contributor.authorMarkopoulou, S.en
dc.contributor.authorTzavaras, T.en
dc.contributor.authorGonos, E. S.en
dc.date.accessioned2015-11-24T19:33:21Z
dc.date.available2015-11-24T19:33:21Z
dc.identifier.issn0003-9861-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/23527
dc.rightsDefault Licence-
dc.subjectApoptosis/drug effects/*physiologyen
dc.subjectCell Line, Transformeden
dc.subjectClusterin/*physiologyen
dc.subjectCyclin-Dependent Kinase Inhibitor p21/*physiologyen
dc.subjectDiploidyen
dc.subjectDown-Regulationen
dc.subjectFibroblasts/drug effects/*physiologyen
dc.subjectHumansen
dc.subjectKeratinocytes/drug effects/*physiologyen
dc.subjectMutationen
dc.subjectProto-Oncogene Proteins c-bcl-2/*physiologyen
dc.subjectSignal Transductionen
dc.subjectSphingosine/*analogs & derivatives/pharmacology/physiologyen
dc.subjectTumor Suppressor Protein p53/*physiologyen
dc.titleBcl-2 but not clusterin/apolipoprotein J protected human diploid fibroblasts and immortalized keratinocytes from ceramide-induced apoptosis: role of p53 in the ceramide responseen
heal.abstractThe role of clusterin/apolipoprotein J (Clu/ApoJ) and Bcl-2 on C(2)-ceramide-induced apoptosis of embryonic human diploid fibroblasts, MRC-5 and immortalized adult skin keratinocytes, HaCaT was investigated. C(2)-ceramide-induced apoptosis of HaCaT in a time- and dose-dependent manner, while in MRC-5 only at higher concentrations. There was a dose-dependent accumulation of Clu/ApoJ and downregulation of Bcl-2 which correlated with C(2)-ceramide-induced apoptosis of MRC-5. While overexpression of Bcl-2 suppressed C(2)-ceramide-mediated apoptosis in both cell types, Clu/ApoJ failed to do so, accessed by morphological changes, DNA fragmentation and PARP cleavage. There was no change in the expression of endogenous p53 or p21(Waf1/Cip1) upon C(2)-ceramide treatment of MRC-5. However, mutant p53(143ala) increased the sensitivity of MRC-5 to C(2)-ceramide-induced apoptosis by markedly downregulating Bcl-2, pointing to a role for p53. These results suggested that whereas downregulation of Bcl-2 may be a crucial factor involved in C(2)-ceramide-induced apoptosis, accumulation of Clu/ApoJ may be a signal of stress response. Moreover, the ceramide-activated apoptotic pathway may be regulated by p53.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1016/j.abb.2005.10.006-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/16297852-
heal.identifier.secondaryhttp://ac.els-cdn.com/S0003986105004145/1-s2.0-S0003986105004145-main.pdf?_tid=8ff0299288a07b9396ac8baaa05c5d8a&acdnat=1333006979_c6de54627958541b4b3f69abe5013f73-
heal.journalNameArch Biochem Biophysen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2006-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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