Modulation of cellular functions by polyamines through polyamine interaction with RNA and proteins

多胺通过多胺与 RNA 和蛋白质相互作用调节细胞功能

• 批准号: 14370739
• 负责人: IGARASHI Kazuei
• 金额: $ 9.02万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370739/
• 关键词: Polyamine; Spermidine; Spermine; Modulon; RF2; Frameshift; NMDA receptor; R-domain; σ^<38>; アンチザイム; イフェンプロジル

1.Synthesis of specific proteins such as OppA, Cya and RpoS (σ^<38>), which are important for cell growth and viability, is stimulated by polyamines at the level of translation in E. coli. In this study, we found that synthesis of Fecl and Fis was also stimulated by polyamines at the level of translation. Fecl and Fis proteins enhance expression of mRNAs involved in iron uptake and energy metabolism, and of rRNA and some tRNAs. When the Shine-Dalgarno (SD) sequences were created at the normal position on these mRNAs, protein synthesis was no longer influenced by polyamines. Thus, the common characteristic of these mRNAs was to have a weak or ineffective SD sequence. We propose that a group of genes whose expression is enhanced by polyamines at the level of translation is referred to as a "polyamine modulon".2.Effect of polyamines on frameshift during translation in E. coli was studied. Frameshift at the 26th termination codon in the open reading frame of RF2 mRNA was stimulated by polyamines in in vivo and in vitro experimental systems. Stimulation occurred at the early logarithmic phase of cell growth, in which the ratio of RF2 mRNA to RF2 protein is high. Polyamines functioned at the decoding site on ribosomes.3.Cycling of polyamines (spermine and spermidine) in the brain was examined by measuring polyamine transport in synaptic vesicles, synaptosomes and glial cells, and the release of spermine from hippocampal slices. It was found that membrane potential-dependent polyamine transport systems exist in synaptosomes and glial cells, and a proton gradient-dependent polyamine transport system exists in synaptic vesicles. Spermine was found to be accumulated in synaptic vesicles and was released from rat hippocampal slices by depeolarization using a high concentration of KCl. Polyamines, in particular spermine, may function as neuromodulators in the brain.

1.在<38>大肠杆菌中，多胺在翻译水平上刺激对细胞生长和活力重要的特定蛋白质如OppA、Cya和RpoS（σ^）的合成。杆菌在本研究中，我们发现，Fecl和Fis的合成也被多胺在翻译水平上刺激。Fecl和Fis蛋白增强参与铁摄取和能量代谢的mRNA以及rRNA和一些tRNA的表达。当Shine-Dalgarno（SD）序列在这些mRNA的正常位置产生时，蛋白质合成不再受多胺的影响。因此，这些mRNA的共同特征是具有弱或无效的SD序列。我们认为，在翻译水平上，多胺能增强一组基因的表达，这组基因被称为“多胺调节子”。大肠杆菌进行了研究。在体内和体外实验系统中，多胺刺激RF 2 mRNA开放阅读框中第26位终止密码子的移码。刺激发生在细胞生长的对数期早期，此时RF 2 mRNA与RF 2蛋白的比例较高。多胺在核糖体上的解码位点发挥作用。3.通过测量多胺在突触囊泡、突触体和胶质细胞中的转运以及海马脑片精胺的释放来研究多胺（精胺和亚精胺）在脑内的循环。结果发现，突触体和神经胶质细胞中存在膜电位依赖的多胺转运系统，突触囊泡中存在质子梯度依赖的多胺转运系统。精胺被发现是积累在突触囊泡和释放大鼠海马脑片使用高浓度的KCl去极化。多胺，特别是精胺，可能在大脑中起神经调质的作用。

项目成果

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