Human oligodendroglial cell line, MO3.13, can be protected from apoptosis using the general caspase inhibitor zVAD-FMK

Recent evidence suggests that the oligodendrocyte cell loss observed in mul tiple sclerosis sufferers is in part mediated by apoptosis, Here we use a h uman cell line, MO3.13, as a model system to investigate the biochemical pr ocesses involved in oligodendroglial cell death. Treatment with staurospori ne kills both naive and differentiated cells in a dose-dependent manner; ho wever, much higher concentrations of staurosporine are required to kill dif ferentiated cells compared to their naive progenitors. Dying cells displaye d the typical morphological characteristics of apoptosis, including cell sh rinkage and chromatin condensation. Biochemical analysis showed that caspas es, a group of enzymes intimately involved in the execution of apoptosis, a re activated in both naive and differentiated cells. Western blotting analy sis revealed that similar subsets of caspase enzymes were operating and tha t the substrate cleavage patterns were identical in both naive and differen tiated cells, Treatment of MO3.13 cells with the general caspase inhibitor zVAD-FMK protected them from toxin-induced cell death. These results indica te that when an oligodendroglial human cell line is exposed to toxin it die s in an apoptotic manner. In addition, we show that cells can be protected from toxin-induced death using an appropriate inhibitor, J, Neurosci, Res. 56:236-243, 1999, (C) 1999 Wiley-Liss, Inc.