PMID- 12163468 OWN - NLM STAT- MEDLINE DCOM- 20020909 LR - 20181113 IS - 0021-9525 (Print) IS - 1540-8140 (Electronic) IS - 0021-9525 (Linking) VI - 158 IP - 3 DP - 2002 Aug 5 TI - c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation. PG - 453-61 AB - Sympathetic neurons depend on NGF binding to TrkA for their survival during vertebrate development. NGF deprivation initiates a transcription-dependent apoptotic response, which is suggested to require activation of the transcription factor c-Jun. Similarly, apoptosis can also be induced by selective activation of the p75 neurotrophin receptor. The transcriptional dependency of p75-mediated cell death has not been determined; however, c-Jun NH2-terminal kinase has been implicated as an essential component. Because the c-jun-null mutation is early embryonic lethal, thereby hindering a genetic analysis, we used the Cre-lox system to conditionally delete this gene. Sympathetic neurons isolated from postnatal day 1 c-jun-floxed mice were infected with an adenovirus expressing Cre recombinase or GFP and analyzed for their dependence on NGF for survival. Cre immunopositive neurons survived NGF withdrawal, whereas those expressing GFP or those uninfected underwent apoptosis within 48 h, as determined by DAPI staining. In contrast, brain-derived neurotrophic factor (BDNF) binding to p75 resulted in an equivalent level of apoptosis in neurons expressing Cre, GFP, and uninfected cells. Nevertheless, cycloheximide treatment prevented BDNF-mediated apoptosis. These results indicate that whereas c-jun is required for apoptosis in sympathetic neurons on NGF withdrawal, an alternate signaling pathway must be induced on p75 activation. FAU - Palmada, M AU - Palmada M AD - Department of Biology, University of California, San Diego, 92138, USA. FAU - Kanwal, S AU - Kanwal S FAU - Rutkoski, N J AU - Rutkoski NJ FAU - Gustafson-Brown, C AU - Gustafson-Brown C FAU - Johnson, R S AU - Johnson RS FAU - Wisdom, R AU - Wisdom R FAU - Carter, B D AU - Carter BD LA - eng GR - R01 NS038220/NS/NINDS NIH HHS/United States GR - NS38220/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20020805 PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Indicators and Reagents) RN - 0 (Luminescent Proteins) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (Receptor, Nerve Growth Factor) RN - 0 (Viral Proteins) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 9061-61-4 (Nerve Growth Factor) RN - 98600C0908 (Cycloheximide) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) SB - IM EIN - J Cell Biol. 2003 Apr 28;161(2):following 439. Gufstafson-Brown, C [corrected to Gustafson-Brown, C] MH - Animals MH - Apoptosis/drug effects/*physiology MH - Base Sequence/genetics MH - Brain-Derived Neurotrophic Factor/metabolism/pharmacology MH - Cells, Cultured MH - Cycloheximide/pharmacology MH - Gene Expression Regulation, Developmental/drug effects/*physiology MH - Genetic Vectors/genetics MH - Green Fluorescent Proteins MH - Immunohistochemistry MH - Indicators and Reagents MH - Integrases/genetics MH - Luminescent Proteins MH - Mice MH - Mice, Knockout MH - Mutation/drug effects/physiology MH - Nerve Growth Factor/*deficiency/genetics MH - Neurons/cytology/drug effects/*metabolism MH - Protein Synthesis Inhibitors/pharmacology MH - Proto-Oncogene Proteins c-jun/*deficiency/genetics MH - Receptor, Nerve Growth Factor/drug effects/*metabolism MH - Superior Cervical Ganglion/cytology/*embryology/growth & development MH - Transfection MH - Viral Proteins/genetics PMC - PMC2173823 EDAT- 2002/08/07 10:00 MHDA- 2002/09/11 10:01 PMCR- 2003/02/05 CRDT- 2002/08/07 10:00 PHST- 2002/08/07 10:00 [pubmed] PHST- 2002/09/11 10:01 [medline] PHST- 2002/08/07 10:00 [entrez] PHST- 2003/02/05 00:00 [pmc-release] AID - jcb.200112129 [pii] AID - 200112129 [pii] AID - 10.1083/jcb.200112129 [doi] PST - ppublish SO - J Cell Biol. 2002 Aug 5;158(3):453-61. doi: 10.1083/jcb.200112129. Epub 2002 Aug 5.