Neutralizing anti-p21ras 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 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 p21ras 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 p21ras protein activity.
Nobes
C D
CD
Department of Human Anatomy, University of Oxford, UK.
Tolkovsky
A M
AM
D000818:Animals; D000937:Antigen-Antibody Reactions; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016283:Proto-Oncogene Proteins p21(ras) / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology*
D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D006131:Growth Inhibitors; D007140:Immunoglobulin Fab Fragments; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D016283:Proto-Oncogene Proteins p21(ras)