Caspases mediate C2-ceramide-induced apoptosis of the human oligodendroglial cell line, MO3.13

The signalling molecule ceramide participates in the sphingomyelin pathway and accumulates intracellularly in response to inflammatory mediators. Here we show that membrane permeable C-2-ceramide is apoptogenic in the immortalised human oligodendroglial cell fine M03.13. Apoptosis (defined by cell shrinkage and chromatin condensation) is accompanied by caspase enzyme activation. Immunoblotting analysis of extracts from differentiated M03.13 cells revealed the presence of caspase-3 proenzyme, activation by cleavage of pro-caspase-3 in cells treated with C-2-ceramide and cleavage of the caspase substrates fodrin and rabaptin. Lysates also showed cleavage of a fluorogenic peptide substrate. Addition of the general caspase inhibitor BAF markedly attenuated apoptosis of M03.13 oligodendroglia. A role for caspase-3-like enzymes in ceramide-induced apoptosis of oligodendroglia may have important implications for approaches to treatment of demyelinating diseases. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.