Activation of cell cycle regulatory proteins in the apoptosis of terminally differentiated oligodendrocytes.

There is increasing evidence that proteins normally involved in the cell cycle play a role in the regulation of neuronal apoptotic death following various insults. However, it is not clear if the same mechanisms regulate cell death of oligodendrocytes as well. In this study, we investigated the mechanism of ceramide-induced apoptosis in primary rat oligodendrocytes. We show that ceramide treatment initiates a cascade of biochemical events involving cell cycle regulatory proteins. Although at the time of induction of cell death the oligodendrocytes are postmitotic, activation of c-myc and translocation of Cdc25A into the nucleus can be demonstrated. Of particular interest are the findings of the up-regulation of PCNA and down-regulation of p21WAF1/CIP1 protein, an inhibitor of cell-cycle progression. The current results show that activation of regulatory cell-cycle proteins at the oligodendrocytes G1-S checkpoint may constitute a crucial step of the death pathway of oligodendrocytes.