| dc.contributor.author | Garcia-Belinchón, Mercè | |
| dc.contributor.author | Sánchez Osuna, María | |
| dc.contributor.author | Martínez Escardó, Laura | |
| dc.contributor.author | Granados-Colomina, Carla | |
| dc.contributor.author | Pascual-Guiral, Sònia | |
| dc.contributor.author | Iglesias-Guimarais, Victoria | |
| dc.contributor.author | Casanelles, Elisenda | |
| dc.contributor.author | Ribas i Fortuny, Judit | |
| dc.contributor.author | Yuste Mateos, Víctor J. (Víctor José) | |
| dc.date.accessioned | 2016-05-02T10:02:01Z | |
| dc.date.available | 2016-05-02T10:02:01Z | |
| dc.date.issued | 2015 | |
| dc.identifier.issn | 0021-9258 | |
| dc.identifier.uri | http://hdl.handle.net/10459.1/56934 | |
| dc.description.abstract | Apoptosis 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.sponsorship | This 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.iso | eng | ca_ES |
| dc.publisher | American Society for Biochemistry and Molecular Biology | ca_ES |
| dc.relation | MICINN/PN2008-2011/SAF2011-24081 | |
| dc.relation | MICINN/PN2008-2011/SAF2012-31485 | |
| dc.relation.isformatof | Reproducció del document publicat a https://doi.org/10.1074/jbc.M115.644179 | ca_ES |
| dc.relation.ispartof | Journal of Biological Chemistry, 2015, vol. 290, p. 20841–20855 | ca_ES |
| dc.rights | (c) American Society for Biochemistry and Molecular Biology, 2015 | ca_ES |
| dc.title | An early and robust activation of caspases heads cells for a regulated form of necrotic-like cell death | ca_ES |
| dc.type | article | ca_ES |
| dc.identifier.idgrec | 023302 | |
| dc.type.version | publishedVersion | ca_ES |
| dc.rights.accessRights | info:eu-repo/semantics/restrictedAccess | ca_ES |
| dc.identifier.doi | https://doi.org/10.1074/jbc.M115.644179 | |
| dc.date.embargoEndDate | 2025-01-01 | |
