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 (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.
Tabuchi
A
A
Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, Department of Biological Chemistry, Sugitani 2630, Toyama 930-0194, Japan.
Nakaoka
R
R
Amano
K
K
Yukimine
M
M
Andoh
T
T
Kuraishi
Y
Y
Tsuda
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000494:pharmacology*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium