Transcriptional coupling of synaptic transmission and energy metabolism: role of nuclear respiratory factor 1 in co-regulating neuronal nitric oxide synthase and cytochrome c oxidase genes in neurons.
Transcriptional coupling of synaptic transmission and energy metabolism: role of nuclear respiratory factor 1 in co-regulating neuronal nitric oxide synthase and cytochrome c oxidase genes in neurons.
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DOI：
10.1016/j.bbamcr.2009.07.001
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Wong-Riley MT
中科院分区：
文献类型：
--
作者：
Dhar SS;Liang HL;Wong-Riley MT
神经元活动高度依赖于能量代谢；然而，传统上这两个过程被认为在转录水平上独立调控。最近，我们发现相同的转录因子核呼吸因子 1 (NRF-1) 共同调节重要的能量产生酶、细胞色素 C 氧化酶以及谷氨酸能受体的关键亚基。本研究检验了我们的假设，即共同调节延伸到谷氨酸能突触的下一个水平，即神经元一氧化氮合酶，它产生一氧化氮作为下游信号分子。使用计算机分析、电泳迁移率变动测定、染色质免疫沉淀、启动子突变和 NRF-1 沉默，我们证明 NRF-1 在功能上与 Nos1 基因启动子结合，但不与 Nos2（诱导型）和 Nos3（内皮型）基因启动子结合。 COX 和 Nos1 转录物均通过去极化 KCl 处理上调，并通过 TTX 介导的神经元脉冲阻断下调。然而，NRF-1 沉默阻断了 KCl 去极化诱导的 Nos1 和 COX 的上调，而 NRF-1 的过表达则挽救了 TTX 下调的 Nos1 和 COX 转录本。这些发现与我们的假设一致，即突触神经元传递和能量代谢在分子水平上紧密耦合。
Neuronal activity is highly dependent on energy metabolism; yet, the two processes have traditionally been regarded as independently regulated at the transcriptional level. Recently, we found that the same transcription factor, nuclear respiratory factor 1 (NRF-1) co-regulates an important energy-generating enzyme, cytochrome c oxidase, as well as critical subunits of glutamatergic receptors. The present study tests our hypothesis that the co-regulation extends to the next level of glutamatergic synapses, namely, neuronal nitric oxide synthase, which generates nitric oxide as a downstream signaling molecule. Using in silico analysis, electrophoretic mobility shift assay, chromatin immunoprecipitation, promoter mutations, and NRF-1 silencing, we documented that NRF-1 functionally bound to Nos1, but not Nos2 (inducible) and Nos3 (endothelial) gene promoters. Both COX and Nos1 transcripts were up-regulated by depolarizing KCl treatment and down-regulated by TTX-mediated impulse blockade in neurons. However, NRF-1 silencing blocked the up-regulation of both Nos1 and COX induced by KCl depolarization, and over-expression of NRF-1 rescued both Nos1 and COX transcripts downregulated by TTX. These findings are consistent with our hypothesis that synaptic neuronal transmission and energy metabolism are tightly coupled at the molecular level.
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DOI：
10.1006/bbrc.1996.0008
发表时间：
1996-01-05
影响因子：
3.1
作者：
Bates, TE;Loesch, A;Clark, JB
通讯作者：
Clark, JB
影响因子：
4.8
作者：
Dhar, Shilpa S.;Ongwijitwat, Sakkapol;Wong-Riley, Margaret T. T.
通讯作者：
Wong-Riley, Margaret T. T.
影响因子：
4.4
作者：
Bros, M;Boissel, JP;Förstermann, U
通讯作者：
Förstermann, U
影响因子：
3.7
作者：
Barthel, Kristen K. B.;Liu, Xuedong
通讯作者：
Liu, Xuedong
影响因子：
5.3
作者：
Gutsaeva, Diana R.;Carraway, Martha Sue;Piantadosi, Claude A.
通讯作者：
Piantadosi, Claude A.