NEUTRALIZING ANTI-P21(RAS) FABS SUPPRESS RAT SYMPATHETIC NEURON SURVIVAL INDUCED BY NGF, LIF, CNTF AND CAMP

In purified cultures of newly isolated rat sympathetic neurons plated on laminin, apoptosis is suppressed by the cytokines leukaemia inhibit ory factor (LIF) and ciliary neurotrophic factor (CNTF), by the permea nt cAMP analogue 8-(4-chloropheny]thio)cAMP, and by nerve growth facto r. Whilst nerve growth factor, 8-(4-chlorophenylthio)cAMP and LIF/CNTF initiate survival by using different kinases, in each case survival i s inhibited by a Fab fragment of Y13-259, a neutralizing antibody to p 21ras proteins, but not by rat IgG Fab. The inhibitory effect of Y13-2 59 could be partially attenuated by cotrituration of the Fab with T'24 (inactive)ras. Thus, prevention of apoptosis in rat sympathetic neuron s by several different survival factors appears to be critically depen dent on p21ras protein activity.