Differential Activation of Brain-derived Neurotrophic Factor Gene Promoters I and III by Ca2+ Signals Evoked vial-type Voltage-dependent andN-Methyl-d-aspartate Receptor Ca2+Channels

Akiko Tabuchi,Ryuki Nakaoka,Kenji Amano,Masaru Yukimine,Tsugunobu Andoh,Yasushi Kuraishi,Masaaki Tsuda

doi:10.1074/jbc.m909538199

Akiko Tabuchi, Ryuki Nakaoka + Show 5 more

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https://doi.org/10.1074/jbc.m909538199

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Journal: Journal of Biological Chemistry	Publication Date: Jun 1, 2000
Citations: 139	License type: cc-by

Abstract

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.

Highlights

The brain-derived neurotrophic factor (BDNF) gene is activated by the intracellular Ca2؉ signals evoked via Ca2؉ influx into neurons, little is known about how the activation of alternative BDNF gene promoters is controlled by the Ca2؉ signals evoked via Nmethyl-D-aspartate receptors (NMDA-R) and L-type voltage-dependent Ca2؉ channels (L-VDCC)
Among the many possible roles of alternative promoters, such as varying the efficiency of transcription initiation, varying the turnover or translation efficiency of mRNA isoforms with different leader exons, changing the tissue specificity, reacting differentially to some extracellular signals, developmentally regulating gene expression, and generating protein isomers differing at the amino terminus, it has been suggested that the alternative promoters of the BDNF gene are involved in the control of tissue- and brain region-specific expression of the gene [9]
Because it has well been established that the expression of the BDNF gene can be controlled by the intracellular Ca2ϩ signals [2, 11, 12, 18], we focused on the effect of the Ca2ϩ signals evoked via L-VDCC and NMDA-R on the alternative BDNF gene promoters

Summary

Introduction

The brain-derived neurotrophic factor (BDNF) gene is activated by the intracellular Ca2؉ signals evoked via Ca2؉ influx into neurons, little is known about how the activation of alternative BDNF gene promoters is controlled by the Ca2؉ signals evoked via Nmethyl-D-aspartate receptors (NMDA-R) and L-type voltage-dependent Ca2؉ 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.

Results

Conclusion