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dc.contributor.authorGarcia-Belinchón, Mercè
dc.contributor.authorSánchez Osuna, María
dc.contributor.authorMartínez Escardó, Laura
dc.contributor.authorGranados-Colomina, Carla
dc.contributor.authorPascual-Guiral, Sònia
dc.contributor.authorIglesias-Guimarais, Victoria
dc.contributor.authorCasanelles, Elisenda
dc.contributor.authorRibas i Fortuny, Judit
dc.contributor.authorYuste Mateos, Víctor J. (Víctor José)
dc.date.accessioned2016-05-02T10:02:01Z
dc.date.available2016-05-02T10:02:01Z
dc.date.issued2015
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/10459.1/56934
dc.description.abstractApoptosis is triggered by the activation of caspases and characterized by chromatin condensation and nuclear fragmentation (type II nuclear morphology). Necrosis is depicted by a gain in cell volume (oncosis), swelling of organelles, plasma membrane leakage, and subsequent loss of intracellular contents. Although considered as different cell death entities, there is an overlap between apoptosis and necrosis. In this sense, mounting evidence suggests that both processes can be morphological expressions of a common biochemical network known as “apoptosis- necrosis continuum.” To gain insight into the events driving the apoptosis-necrosis continuum, apoptotically proficient cells were screened facing several apoptotic inducers for the absence of type II apoptotic nuclear morphologies. Chelerythrine was selected for further studies based on its cytotoxicity and the lack of apoptotic nuclear alterations. Chelerythrine triggered an early plasma membrane leakage without condensed chromatin aggregates. Ultrastructural analysis revealed that chelerythrine-mediated cytotoxicity was compatible with a necrotic-like type of cell death. Biochemically, chelerythrine induced the activation of caspases. Moreover, the inhibition of caspases prevented chelerythrine-triggered necrotic-like cell death. Compared with staurosporine, chelerythrine induced stronger caspase activation detectable at earlier times. After using a battery of chemicals, we found that high concentrations of thiolic antioxidants fully prevented chelerythrine-driven caspase activation and necrotic-like cell death. Lower amounts of thiolic antioxidants partially prevented chelerythrine-mediated cytotoxicity and allowed cells to display type II apoptotic nuclear morphology correlating with a delay in caspase-3 activation. Altogether, these data support that an early and pronounced activation of caspases can drive cells to undergo a form of necrotic-like regulated cell death.ca_ES
dc.description.sponsorshipThis work was supported in part by Ministerio de Ciencia e Innovación/ Fondo Europeo de Desarrollo Regional (MICINN/FEDER) Grant SAF2011- 24081, Ministerio de Economía y Competitividad/FEDER Grant SAF2012- 31485, and Generalitat de Catalunya Grants 2009-SGR-346 and 2014-SGR- 1609.ca_ES
dc.language.isoengca_ES
dc.publisherAmerican Society for Biochemistry and Molecular Biologyca_ES
dc.relationMICINN/PN2008-2011/SAF2011-24081
dc.relationMICINN/PN2008-2011/SAF2012-31485
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1074/jbc.M115.644179ca_ES
dc.relation.ispartofJournal of Biological Chemistry, 2015, vol. 290, p. 20841–20855ca_ES
dc.rights(c) American Society for Biochemistry and Molecular Biology, 2015ca_ES
dc.titleAn early and robust activation of caspases heads cells for a regulated form of necrotic-like cell deathca_ES
dc.typearticleca_ES
dc.identifier.idgrec023302
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1074/jbc.M115.644179
dc.date.embargoEndDate2025-01-01


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