H. Yaginuma et al., Caspase activity is involved in, but is dispensable for, early motoneuron death in the chick embryo cervical spinal cord, MOL CELL NE, 18(2), 2001, pp. 168-182
We examined the role of caspases in the early programmed cell death (PCD) o
f motoneurons (MNs) in the chick embryo cervical cord between embryonic day
(E) 4 and E5. An increase in caspase-3-like activity in MNs was observed a
t E4.5. Treatment with an inhibitor of caspase-3-like activity, Ac-DEVD-CHO
, for 12 h blocked this increase and revealed that caspase-3-like activity
is mainly responsible for DNA fragmentation and the nuclear changes during
PCD but not for degenerative changes in the cytoplasm. When a more broad-sp
ectrum caspase inhibitor was used (bocaspartyl (OMe)-fluoromethyl ketone, B
AF), the appearance of degenerative changes in the cytoplasm was delayed by
at least 12 h. However, following treatment with either Ac-DEVD-CHO or BAF
for 24 h, the number of surviving healthy MNs did not differ from controls
, indicating a normal occurrence of PCD despite the inhibition of caspases.
These results suggest that caspase cascades that occur upstream of and are
independent of the activation of caspase-3-like activity are responsible f
or the degenerative changes in the cytoplasm of dying cervical MNs. These d
ata also suggest that, although one function of caspases may be to facilita
te the kinetics of PCD, caspases are nonetheless dispensable for at least s
ome forms of normal neuronal PCD in vivo.