PMID- 18198284
OWN - NLM
STAT- MEDLINE
DCOM- 20080403
LR  - 20080318
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Linking)
VI  - 73
IP  - 4
DP  - 2008 Apr
TI  - Salicylate alters the expression of calcium response transcription factor 1 in 
      the cochlea: implications for brain-derived neurotrophic factor transcriptional 
      regulation.
PG  - 1085-91
LID - 10.1124/mol.107.041814 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is a key neurotrophin whose expression 
      is altered in response to neurological activity, influencing both short- and 
      long-term synaptic changes. The BDNF gene consists of eight upstream exons 
      (I-VII), each of which has a distinct promoter and can be independently spliced 
      to the ninth coding exon (IX). We showed recently that the expression of BDNF 
      exon IV in the cochlea is altered after exposure to salicylate, an ototoxic drug 
      that in high doses is able to induce hearing loss and tinnitus. These changes 
      were a crucial trigger for plasticity changes in the central auditory system. 
      BDNF exon IV expression is regulated via interaction between calcium-response 
      elements CaRE1, CaRE2, and CaRE3/Cre (CaREs) that are bound by the transcription 
      factors CaRF1, upstream stimulatory factors 1 and 2 (USF1/2), and cAMP/Ca(2+) 
      response element-binding protein (CREB), respectively. To determine whether the 
      salicylate-induced changes in cochlear BDNF exon IV expression include a 
      differential use of the CaRE binding proteins, we studied the level of the 
      corresponding binding proteins in the spiral ganglion neurons before and after 
      systemic application of concentrated salicylate using in situ hybridization and 
      RT-PCR. BDNF exon IV and CaRF1 expression were up-regulated after application of 
      salicylate, whereas USF1/2 and CREB mRNA expression remained unaffected. The 
      changes in BDNF exon IV and CaRF1 expression were also dose-dependent. The data 
      show Ca(2+) and CaRF1 as messengers of trauma (salicylate)-induced altered BDNF 
      levels in the cochlea. Furthermore, they also provide the first evidence that a 
      differential regulation of BDNF transcription factors might participate in 
      BDNF-mediated plasticity changes.
FAU - Singer, Wibke
AU  - Singer W
AD  - HNO-Klinik, Universitat Tubingen, Elfriede-Aulhorn-Strasse 5, D-72076 Tubingen, 
      Germany.
FAU - Panford-Walsh, Rama
AU  - Panford-Walsh R
FAU - Watermann, Dirk
AU  - Watermann D
FAU - Hendrich, Oliver
AU  - Hendrich O
FAU - Zimmermann, Ulrike
AU  - Zimmermann U
FAU - Kopschall, Iris
AU  - Kopschall I
FAU - Rohbock, Karin
AU  - Rohbock K
FAU - Knipper, Marlies
AU  - Knipper M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080115
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Salicylates)
RN  - 0 (Transcription Factors)
RN  - 0 (calcium response transcription factor 1, rat)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cochlea/cytology/*drug effects/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Exons/genetics
MH  - Female
MH  - Gene Expression Regulation/*drug effects
MH  - In Situ Hybridization
MH  - Injections
MH  - Neurons/drug effects/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Binding/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Response Elements
MH  - Salicylates/*pharmacology
MH  - Transcription Factors/*genetics/metabolism
MH  - Transcription, Genetic/*drug effects
EDAT- 2008/01/17 09:00
MHDA- 2008/04/04 09:00
CRDT- 2008/01/17 09:00
PHST- 2008/01/17 09:00 [pubmed]
PHST- 2008/04/04 09:00 [medline]
PHST- 2008/01/17 09:00 [entrez]
AID - mol.107.041814 [pii]
AID - 10.1124/mol.107.041814 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2008 Apr;73(4):1085-91. doi: 10.1124/mol.107.041814. Epub 2008 Jan 
      15.