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Keywords:

  • apoptosis;
  • histones;
  • rat superior cervical ganglion;
  • tyrosine phosphorylation;
  • PKA

Abstract

In purified cultures of newly isolated rat sympathetic neurons plated on laminin, apoptosis is suppressed by the cytokines leukaemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF), by the permeant cAMP analogue 8-(4-chlorophenylthio)cAMP, and by nerve growth factor. Whilst nerve growth factor, 8-(4-chlorophenylthio) cAMP and LIF/CNTF initiate survival by using different kinases, in each case survival is inhibited by a Fab fragment of Y13-259, a neutralizing antibody to p2lras proteins, but not by rat IgG Fab. The inhibitory effect of Y13-259 could be partially attenuated by cotrituration of the Fab with T′24(inactive)ras. Thus, prevention of apoptosis in rat sympathetic neurons by several different survival factors appears to be critically dependent on p21 ras protein activity.