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C 2 ‐ceramide mediates cerebellar granule cells apoptosis by activation of caspases‐2, ‐9, and ‐3
Author(s) -
Miñano Alfredo,
CaballeroBenítez Andrea,
Lluch Mónica,
Morán Julio,
RodríguezAlvarez José
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21633
Subject(s) - ceramide , apoptosis , caspase , microbiology and biotechnology , chemistry , granule (geology) , cerebellum , neuroscience , biology , programmed cell death , biochemistry , paleontology
Ceramide is able to induce the apoptotic death of cerebellar granule cells (CGC) in culture. However, previous reports did not agree on whether ceramide‐induced apoptosis of CGC requires caspase activation. Here we have shown that addition of C 2 ‐ceramide is able to produce extensive death of cultured CGC, which is associated with chromatin condensation, ladder‐like DNA fragmentation, and activation of caspases. Our results show that C 2 ‐ceramide activates caspases‐3, ‐9, and ‐2 but not caspases‐1 and ‐8. Caspase‐9 activation was associated with cytochrome c release from mitochondria toward the cytosol and was followed by activation of caspases‐2 and ‐3. PARP proteolysis was also observed after caspase‐3 and ‐2 activation. The involvement of caspases‐9, ‐3, and ‐2 in ceramide‐mediated apoptotic death of CGC was further supported by the use of specific inhibitors. © 2008 Wiley‐Liss, Inc.