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
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
复制标题
DOI：
10.1074/jbc.m909538199
复制
发表时间：
2000-06-09
影响因子：
4.8
通讯作者：
Tsuda, M
中科院分区：
文献类型：
--
作者：
Tabuchi, A;Nakaoka, R;Tsuda, M
虽然脑源性神经营养因子（BDNF）基因是由细胞内Ca 2+信号激活的，但对BDNF基因启动子的激活如何由N-甲基-D-天冬氨酸受体（NMDA-R）和L型电压依赖性Ca 2+通道（L-VDCC）引起的Ca 2+信号控制知之甚少，高K+浓度（25-50 mM KCl）引起的膜去极化存在一个临界范围，用于大鼠皮层培养物中BDNF mRNA的有效表达和BDNF基因启动子I和III（分别为BDNF-PI和-PIII）的转录激活。高K+诱导的BDNF mRNA表达的增加不仅被L-VDCC拮抗剂尼卡地平抑制，而且被NMDA-R拮抗剂DL-氨基-5-膦酰基戊酸抑制，这被拮抗剂对Ca ~（2+）内流的作用所支持。虽然在25和50 mM KCl下启动子激活不同，但BDNF-PIII通过NMDA-R或L-VDCC的Ca 2+内流激活，而BDNF-PI主要通过L-VDCC的Ca 2+内流激活。直接刺激NMDA-R可促进BDNF-PIII的激活，但不支持BDNF-PI的激活。因此，替代BDNF基因启动子对NMDA-R和L-VDCC诱发的细胞内Ca ~（2+）信号的反应不同。
Although 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 N-methyl-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 KCI) 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 Ca2+ influx. Although the promoter activations at 25 and 50 mM KCI were different, BDNF-PIII was activated by either the Ca2+ influx through NMDA-R or L-VDCC, whereas BDNF-PI was predominantly by the Ca2+ 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 Ca2+ signals evoked via NMDA-R and L-VDCC.