BFGF inhibits the activation of caspase-3 and apoptosis of P19 embryonal carcinoma cells during neuronal differentiation

P19 embryonal carcinoma (EC) cells undergo apoptosis during neuronal differ entiation induced by all-trans retinoic acid (RA), Caspase-3-like proteases are activated and involved in the apoptosis of P19 EC cells during neurona l differentiation.(1) Recently it has been shown that growth factor signals protect against apoptosis by phosphorylation of Bad, Phosphorylated Bad, a n apoptotic member of the Bcl-2 family, cannot bind to Bcl-x(L) and results in Bcl-xL homodimer formation and subsequent antiapoptotic activity. In th e present study, we demonstrate that this system is used generally to prote ct against apoptosis during neuronal differentiation. Bcl-xL inhibited the activation of caspase-3-like proteases, Basic fibroblast growth factor (bFG F) inhibited more than 90% of the caspase-3-like activity, inhibited proces sing of caspase-3 into its active form, and inhibited DNA fragmentation. bF GF activated phosphatidyl-inositol-3-kinase (P13K) and stimulated the phosp horylation of Bad. Phosphorylation was inhibited by wortmannin, an inhibito r of P13K and its downstream target Akt, Thus, Bad is a target of the FGF r eceptor-mediated signals involved in the protection against activation of c aspase-3.