Role of caspase-1 subfamily in cytotoxic cytokine-induced oligodendrocyte cell death.
Oligodendrocytes are myelin forming cells in mammalian central nervous system. About 50% of oligodendrocytes (OLGs) undergo cell death in normal development. In addition, OLG cell deaths have been observed in demyelinating diseases including multiple sclerosis ( MS). Clinical observations and in vitro cell culture studies have suggested that cytokines mediate OLG cell damage in multiple sclerosis ( MS). Among the cytokines, tumor necrosis factor (TNF) is thought to be one of the mediators responsible for the damage of OLGs in MS. The administration of TNF-alpha to primary cultures of OLGs induced DNA fragmentation, and significantly decreased the number of live OLGs. Chemical inhibitors Ac-YVAD-CHO (a specific inhibitor of caspase-1 (ICE)-like proteases) enhanced the survival of TNF-alpha treated OLGs better than Ac-DEVD-CHO (a specific inhibitor of caspase-3 (CPP32)-like proteases). These results indicate that caspase-1- mediated cell-death pathway are activated in TNF-induced OLG cell death. Caspase-11 is involved in activation of caspase-1. Oligodendrocytes from caspase-11-deficient mice are partially resistant to TNF-induced OLG cell death. Our results suggest that the inhibition of caspase-1 sufamily may be a novel therapeutic approach to treat MS.[1]References
- Role of caspase-1 subfamily in cytotoxic cytokine-induced oligodendrocyte cell death. Hisahara, S., Takano, R., Shoji, S., Okano, H., Miura, M. J. Neural Transm. Suppl. (2000) [Pubmed]
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