Bcl-xL inhibits different apoptotic pathways in rat PC12 cells

Bcl-x(L,) a member of the bcl-2 family of proteins is required for the survival of neurons early in development. To study the mechanism of action of Bcl-x(L) in a neuronal context, we generated rat PC12 cells overexpressing Bcl-x(L) and examined their susceptibility to apoptotic stimuli that induce apoptosis through different pathways involving trophic-factor deprivation, staurosporine, tumor necrosis factor alpha or cisplatin. Overexpression of Bcl-x(L) in both naive and neuronal PC12 cells inhibited apoptosis induced by the different pathways. However, the extent of this protective effect varied, suggesting that the contribution of the Bcl-x(L)-controlled step to apoptosis differs in the different pathways. Our findings also showed that TNF alpha-induced activation of caspase-3 is inhibited by overexpression of Bcl-x(L), suggesting that Bcl-x(L) acts upstream of caspase activation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.