PMID- 18649393
OWN - NLM
STAT- MEDLINE
DCOM- 20090113
LR  - 20131121
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 56
IP  - 13
DP  - 2008 Oct
TI  - Extracellular adenosine 5'-triphosphate elicits the expression of brain-derived 
      neurotrophic factor exon IV mRNA in rat astrocytes.
PG  - 1369-79
LID - 10.1002/glia.20704 [doi]
AB  - A growing body of recent evidence indicates that ATP plays an important role in 
      neuronal-glial communications. In this study, the authors demonstrated that 
      extracellular ATP elicits the gene expression of brain-derived neurotrophic 
      factor (BDNF), especially BDNF exon IV mRNA, in primary cultured rat cortical 
      astrocytes but not in neurons. To investigate the mechanism by which ATP induces 
      BDNF exon IV mRNA expression, the authors used immortalized astrocyte cell line 
      RCG-12. ATP dose-dependently increased the expression of BDNF exon IV mRNA and 
      activated BDNF promoter IV. P2Y receptor agonists (ADP and 2MeS-ADP) but not a 
      P2X receptor agonist (alphabetaMeATP) induced the expression of BDNF exon IV 
      mRNA. Moreover, ATP-induced BDNF exon IV mRNA upregulation was inhibited by a P2Y 
      antagonist (MRS2179) but not by P2X antagonists (TNP-ATP and PPADS). These 
      findings suggest the involvement of P2Y receptors in the ATP-induced 
      transcription of the BDNF gene. Among the signal transduction inhibiters examined 
      in this study, intracellular Ca(2+) chelator (BAPTA-AM) and 
      Ca(2+)/calmodulin-dependent kinase (CaM kinase) inhibitors (KN-93 and W-7) 
      attenuated ATP-induced BDNF exon IV mRNA upregulation. ATP transiently induced 
      the phosphorylation of cAMP-responsive element-binding protein (CREB). 
      ATP-induced CREB phosphorylation was repressed by P2Y antagonists, BAPTA-AM, and 
      CaM kinase inhibitors. Overexpression of dominant negative CREB mutants reduced 
      the activation of BDNF promoter IV and attenuated the upregulation of BDNF exon 
      IV mRNA expression. These results suggest that ATP induces BDNF expression 
      through P2Y receptor followed by the activation of CaM kinase and CREB in 
      astrocytes. These mechanisms are likely to contribute to the enhancement of 
      neuronal-glial networks.
FAU - Takasaki, Ichiro
AU  - Takasaki I
AD  - Division of Molecular Genetics Research, Life Science Research Center, University 
      of Toyama, Toyama, Japan. takasaki@cts.u-toyama.ac.jp
FAU - Takarada, Satoko
AU  - Takarada S
FAU - Tatsumi, Saori
AU  - Tatsumi S
FAU - Azegami, Aiko
AU  - Azegami A
FAU - Yasuda, Makoto
AU  - Yasuda M
FAU - Fukuchi, Mamoru
AU  - Fukuchi M
FAU - Tabuchi, Akiko
AU  - Tabuchi A
FAU - Kondo, Takashi
AU  - Kondo T
FAU - Tabuchi, Yoshiaki
AU  - Tabuchi Y
FAU - Tsuda, Masaaki
AU  - Tsuda M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/*physiology
MH  - Animals
MH  - Astrocytes/*physiology
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Cells, Cultured
MH  - Exons/*physiology
MH  - Extracellular Space/genetics/*physiology
MH  - Gene Expression Regulation/physiology
MH  - RNA, Messenger/*biosynthesis/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2008/07/24 09:00
MHDA- 2009/01/14 09:00
CRDT- 2008/07/24 09:00
PHST- 2008/07/24 09:00 [pubmed]
PHST- 2009/01/14 09:00 [medline]
PHST- 2008/07/24 09:00 [entrez]
AID - 10.1002/glia.20704 [doi]
PST - ppublish
SO  - Glia. 2008 Oct;56(13):1369-79. doi: 10.1002/glia.20704.