Nerve Growth Factor Determines Survival and Death of PC12 Cells by Regulation of the bcl‐x, bax, and caspase‐3 Genes

: 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 PC12 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 increases in caspase‐3 and bcl‐xs levels should have disposed the cells toward apoptosis but were opposed by the simultaneous increase in bcl‐xl level. NGF withdrawal resulted in abrupt down‐regulation of bcl‐xl and up‐regulation of bax, favoring apoptosis. Forced expression of bcl‐xl after NGF withdrawal was sufficient to prevent cell death. Cell death was rapid when NGF was withdrawn after 5 days of treatment but relatively slow when NGF was withdrawn after only 1 or 2 days of treatment. This was consistent with the reduced accumulation of caspase‐3 mRNA with shorter NGF treatments. These results indicate that Bcl‐xl, Bcl‐xs, Bax, and caspase‐3 are important regulators of apoptosis in PC12 cells. Furthermore, regulation of their mRNA levels is implicated in the signal transduction of NGF.