Mw. Craighead et al., Human oligodendroglial cell line, MO3.13, can be protected from apoptosis using the general caspase inhibitor zVAD-FMK, J NEUROSC R, 57(2), 1999, pp. 236-243
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.