INVOLVEMENT OF THE LOW-AFFINITY NEUROTROPHIN RECEPTOR (P75(NIR)) IN APOPTOSIS OF DIFFERENTIATED PC12 CELLS

Although the function of the low-affinity neurotrophin receptor (p75(N TR)) has not yet been clearly established, there is increasing evidenc e to suggest that it may play a role in determining cell viability ind ependent of an interaction with Trk receptors. In the present study, t he ability of both neurotrophins and antibodies against the p75(NTR) t o rescue differentiated PC12 cells from apoptotic death induced by ser um withdrawal was examined. The results demonstrate that both nerve gr owth factor and a polyclonal antibody to the p75(NTR) effectively resc ued cells from apoptosis. In contrast, brain-derived neurotrophic fact or, a monoclonal p75(NTR) antibody (192-IgG), and non-immune IgG faile d to rescue the differentiated PC12 cells. These results support the h ypothesis that the p75(NTR) can mediate survival of differentiated PC1 2 cells after removal of trophic support independent of Trk receptor a ctivity. These data also demonstrate that occupancy of p75(NTR) only b y specific ligands results in protection against cell death invoked by removal of trophic support. This may be due to select activation of s pecific intracellular cascades which are modulated by p75(NTR) in a li gand-specific manner.