Differential activation of brain-derived neurotrophic factor gene promoters I and III by Ca2+ signals evoked via L-type voltage-dependent and N-methyl-D-aspartate receptor Ca2+ channels

Although the brain-derived neurotrophic factor (BDNF) gene is activated by the intracellular Ca(2+) signals evoked via Ca(2+) influx into neurons, little is known about how the activation of alternative BDNF gene promoters is controlled by the Ca(2+) signals evoked via N-methyl-d-aspartate receptors...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2000-06, Vol.275 (23), p.17269
Main Authors: Tabuchi, A, Nakaoka, R, Amano, K, Yukimine, M, Andoh, T, Kuraishi, Y, Tsuda, M
Format: Article
Language:English
Subjects:
2-Amino-5-phosphonovalerate - pharmacology
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology
Animals
Brain-Derived Neurotrophic Factor - biosynthesis
Brain-Derived Neurotrophic Factor - genetics
Calcium - metabolism
Calcium Channel Blockers - pharmacology
Calcium Channels, L-Type - pharmacology
Calcium Signaling - physiology
Cells, Cultured
Cerebral Cortex - cytology
Cerebral Cortex - physiology
Embryo, Mammalian
Gene Expression Regulation - drug effects
Gene Expression Regulation - physiology
Neurons - physiology
Potassium Chloride - pharmacology
Promoter Regions, Genetic
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate - physiology
Recombinant Fusion Proteins - biosynthesis
Transfection
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although the brain-derived neurotrophic factor (BDNF) gene is activated by the intracellular Ca(2+) signals evoked via Ca(2+) influx into neurons, little is known about how the activation of alternative BDNF gene promoters is controlled by the Ca(2+) signals evoked via N-methyl-d-aspartate receptors (NMDA-R) and L-type voltage-dependent Ca(2+) channels (L-VDCC). There is a critical range in the membrane depolarization caused by high K(+) concentrations (25-50 mm KCl) for effective BDNF mRNA expression and transcriptional activation of BDNF gene promoters I and III (BDNF-PI and -PIII, respectively) in rat cortical culture. The increase in BDNF mRNA expression induced at high K(+) was repressed not only by nicardipine, an antagonist for L-VDCC, but also by dl-amino-5-phosphonovalerate, an antagonist for NMDA-R, which was supported by the effects of antagonists on the Ca(2+) influx. Although the promoter activations at 25 and 50 mm KCl were different, BDNF-PIII was activated by either the Ca(2+) influx through NMDA-R or L-VDCC, whereas BDNF-PI was predominantly by the Ca(2+) influx through L-VDCC. Direct stimulation of NMDA-R supported the activation of BDNF-PIII but not that of BDNF-PI. Thus, the alternative BDNF gene promoters responded differently to the intracellular Ca(2+) signals evoked via NMDA-R and L-VDCC.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M909538199