PMID- 8632149
OWN - NLM
STAT- MEDLINE
DCOM- 19960701
LR  - 20220309
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 66
IP  - 6
DP  - 1996 Jun
TI  - Brain-derived neurotrophic factor stimulates AP-1 and cyclic AMP-responsive 
      element dependent transcriptional activity in central nervous system neurons.
PG  - 2279-86
AB  - Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, 
      regulates survival and apoptosis of several neuronal populations. These effects 
      are initiated by high-affinity membrane receptors displaying tyrosine kinase 
      activity (trk). However, the intracellular pathways and genetic mechanisms 
      associated with these receptors are largely unknown. Here we show that BDNF 
      stimulates AP1 binding activity in primary cerebellar neurons. This binding 
      corresponds to a functional complex as it is associated with the induction of 
      AP1-dependent transactivation. Application of AP1 partner mRNAs shows an increase 
      in levels of c-fos and c-jun mRNAs after BDNF treatment, resulting from an 
      induction of their promoters. The cis-acting elements by which BDNF stimulates 
      c-fos transcription were further studied. We show that BDNF impinges on multiple 
      regulatory elements, including the serum-responsive element, Fos AP1-like 
      element, and cyclic AMP (cAMP)-responsive element (CRE) sequences. The latter was 
      stimulated without any detectable increase in cAMP or Ca2+ levels. To confirm 
      that BDNF induces c-fos transcription independently of the protein kinase A/cAMP 
      pathway, we transfected a dominant inhibitory mutant of the regulatory subunit of 
      protein kinase A. The overexpression of this mutant does not affect the c-fos 
      promoter transactivation by BDNF. In summary, we show that BDNF stimulates AP1- 
      and CRE-dependent transcription through a mechanism that is distinct from the 
      cAMP- and Ca(2+)-dependent pathways in CNS neurons.
FAU - Gaiddon, C
AU  - Gaiddon C
AD  - URA 1446, CNRS, Laboratoire de Physiologie Generale, Universite Louis Pasteur, 
      Strasbourg, France.
FAU - Loeffler, J P
AU  - Loeffler JP
FAU - Larmet, Y
AU  - Larmet Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor
MH  - Calcium/physiology
MH  - Cell Survival/genetics
MH  - Central Nervous System/cytology
MH  - Cerebellum/cytology
MH  - Cyclic AMP/genetics
MH  - Cyclic AMP Response Element-Binding Protein/*genetics
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Genes, Immediate-Early/genetics
MH  - Genes, fos/genetics
MH  - Genes, jun/genetics
MH  - Nerve Growth Factors/*genetics
MH  - Nerve Tissue Proteins/*genetics
MH  - Neurons/cytology/enzymology/*physiology
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding/physiology
MH  - Rats
MH  - Second Messenger Systems/physiology
MH  - Transcription Factor AP-1/*genetics/metabolism
MH  - Transcription, Genetic/genetics
MH  - Transfection
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
AID - 10.1046/j.1471-4159.1996.66062279.x [doi]
PST - ppublish
SO  - J Neurochem. 1996 Jun;66(6):2279-86. doi: 10.1046/j.1471-4159.1996.66062279.x.