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 C2-ceramide is apoptogenic in the immortalised human oligodendroglial cell line MO3.13. Apoptosis (defined by cell shrinkage and chromatin condensation) is accompanied by caspase enzyme activation. Immunoblotting analysis of extracts from differentiated MO3.13 cells revealed the presence of caspase-3 proenzyme, activation by cleavage of pro-caspase-3 in cells treated with C2-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 MO3.13 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.
Craighead
M
M
Division of Neuroscience, Biological Sciences, University of Manchester, UK.
Pole
J
J
Waters
C
C
D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D002461:Cell Line, Transformed; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013049:Spectrin
D002352:Carrier Proteins; D053148:Caspase 3; D020169:Caspases; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D008840:Microfilament Proteins; D013110:Sphingosine; D013049:Spectrin; C064769:N-acetylsphingosine; C505407:CASP3 protein, human