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Moran, J; Minano, A; Caballero-Benitez, A; Lluch, M; Rodriguez-Alvarez, J (2008)

C2-CERAMIDE MEDIATES CEREBELLAR GRANULE CELLS APOPTOSIS BY ACTIVATION OF CASPASES-2,-9, AND-3

J NEUROSCI RES 86(8):1734-1747
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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 C2-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. (c) 2008 Wiley-Liss, Inc.