P. Rong et al., Nerve growth factor determines survival and death of PC12 cells by regulation of the bcl-x, bax, and caspase-3 genes, J NEUROCHEM, 72(6), 1999, pp. 2294-2300
We investigated the effects of nerve growth factor (NGF) and NGF withdrawal
on expression of members of the bcl-2 family of genes and caspase-3 in PC1
2 cells. NGF regulated several members of the bcl-2 family and caspase-3 in
a manner consistent with its effect on apoptosis in PC12 cells. Levels of
bcl-xl, bcl-xs, and caspase-3 mRNAs were increased by NGF treatment. The in
creases in caspase-3 and bcl-xs levels should have disposed the cells towar
d apoptosis but were opposed by the simultaneous increase in bcl-xl level.
NGF withdrawal resulted in abrupt down-regulation of bcl-xl and up-regulati
on of bax, favoring apoptosis. Forced expression of bcl-xl after NGF withdr
awal was sufficient to prevent cell death. Cell death was rapid when NGF wa
s withdrawn after 5 days of treatment but relatively slow when NGF was with
drawn after only 1 or 2 days of treatment. This was consistent with the red
uced accumulation of caspase-3 mRNA with shorter NGF treatments. These resu
lts indicate that Bcl-xl, Bcl-xs, Bar, and caspase-3 are important regulato
rs of apoptosis in PC12 cells. Furthermore, regulation of their mRNA levels
is implicated in the signal transduction of NGF.