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Regulation of Mechanisms underlying signal transduction via sigma-1 receptor and activity of Tyrosine Hydroxylase.

通过 sigma-1 受体和酪氨酸羟化酶活性调节信号转导的机制。

基本信息

批准号：
09680781
负责人：
YAMAMOTO Hideko
金额：
$ 2.11万
依托单位：
Tokyo Institute of Psychiatry
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680781/
关键词：
Tyrosine Hydroxylase V-1 NO sigma-1 receptors c-jun dopamine beta-hydroxylase mutation primary cultured neuronal cells GST融合蛋白質トランスジェニックマウスノルアドレナリンアドレナリン会合蛋白質 Xenopus oocyte 転写因子 CREB

项目摘要

(1). Mechanism underlying signal transduction via intracelluar sigma-1 receptors. Expression cloning of sigma-1 receptor (sR1) in Xenopus oocytes showed a binding ability for NE-100, a ligand of sR1, as observed in native tissues. Site-directed mutagenesis in the putative transmembrane (TN) domain of sR1 did not alter expression levels of mutant sR1. [ィイD13ィエD1H]NE-100 binding was abolished by the double mutation (S99! and LL105-106AA) or by the single mutation (Y103F). Scatchard analysis using [ィイD13ィエD1H](+)pentazocine as a ligand demonstrated that the single mutation (Y103F) resulted in low affinity, however, the double mutation (S99A, LL105-106AA) had no effect. These findings provide evidence that the putative TM domain of sR1 plays a critical role in ligand-binding.(2). Kinetic Characterization of the nitric oxide (NO) toxicity for PC12 cells: effects of half-life time of NO release. Effects of low concentrations of nitric oxide (NO) on cell viability using NO donors. Exposure of … More undifferentiated PC12 cells to low concentrations of NO donors resulted in cell death in a dose- and time-dependent manner. The NO-induced cell death was characterized as apoptosis-like cell death. Pretreatment with an antioxidant ascorbic acid completely prevented the cell death. These findings suggest that the cell toxicity induced by NO at low concentrations strongly depends upon the duration of expose to NO from NO-donors.(3). A novel protein containing cdc 10/SWI6 motifs regulates expression of mRNA encoding catecholamine biosynthesizing enzymes. Mechanisms that control expression of catecholaminergic biosynthesizing enzymes in a transmitter phenotype-specific manner, are poorly understood. We provide evidence that overexpression of a novel cdc10SWI6 motif-containing protein, V-1, elicits the coordinate up-regulation of above enzymes in PC12D, and catecholamine levels are increased. Furthermore, V-1 is strongly expressed in the cytoplasm of rat chromaffin cells of adrenal medulla. Thus, V-1 may act as a cytoplasmic protein/protein adapter and be involved in control of the catecholaminergic phenotype expression via an intracellular pathway signaling to the nucleus. Less

(1)。通过细胞内Sigma-1受体的信号转导机制。Sigma-1受体(SR1)在非洲爪哇卵母细胞中的表达克隆表明，与在天然组织中观察到的一样，SR1的配体NE-100具有结合能力。在SR1假定的跨膜(TN)区域进行定点突变并不改变突变体SR1的表达水平。[ィイD13ィエD1H]NE-100结合被双突变取消(S99！和LL105-106AA)或单一突变(Y103F)。以[ィイD13ィエD1H](+)五唑碱为配基的Scatchard分析表明，单突变(Y103F)导致亲和力低，而双突变(S99A，LL105-106AA)则没有影响。这些发现为推测SR1的TM结构域在配体结合中发挥关键作用提供了证据。一氧化氮(NO)对PC12细胞毒性的动力学特征：NO释放半衰期的影响。低浓度一氧化氮(NO)对使用NO供体的细胞活力的影响。…的曝光更多未分化的PC12细胞对低浓度的NO供体以剂量和时间依赖的方式导致细胞死亡。NO诱导的细胞死亡以凋亡样细胞死亡为特征。用抗氧化剂抗坏血酸进行预处理可以完全阻止细胞死亡。这些发现表明，低浓度NO诱导的细胞毒性强烈依赖于NO供体暴露于NO的时间。一种含有CDC10/SWI6基序的新蛋白调节编码儿茶酚胺生物合成酶的mRNA的表达。以递质表型特异的方式控制儿茶酚胺能生物合成酶表达的机制还知之甚少。我们提供的证据表明，一种新的含有cdc10SWI6基序的蛋白V-1的过表达诱导了PC12D中上述酶的协同上调，儿茶酚胺水平增加。此外，V-1在大鼠肾上腺髓质嗜铬细胞胞浆中呈强阳性表达。因此，V-1可能作为胞质蛋白/蛋白适配器，通过胞内信号通路参与儿茶酚胺能表型表达的调控。较少