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。特异性蛋白（例如OPPA，CYA和RPOS（σ^<38>），对细胞生长和生存力很重要的合成，在大肠杆菌中的翻译水平上刺激了细胞生长和生存力。在这项研究中，我们发现在翻译水平上，多胺还刺激了FECL和FIS的合成。 FECL和FIS蛋白增强了参与铁摄取和能量代谢以及rRNA和一些TRNA的mRNA的表达。当在这些mRNA上的正常位置产生Shine-Dalgarno（SD）序列时，蛋白质合成不再受多胺影响。这是这些mRNA的共同特征是具有弱或无效的SD序列。我们提出，一组基因在翻译水平上通过多胺增强的基因被称为“多胺模元” .2。多胺在大肠杆菌中翻译过程中对帧速率的影响。在体内和体外实验系统中，多胺在RF2 mRNA的开放阅读框架中的第26端密码子处的移截面刺激。刺激发生在细胞生长的早期对数期，其中RF2 mRNA与RF2蛋白的比率很高。多胺在核糖体上的解码位点起作用。3。通过测量突触蔬菜，突触体和神经胶质细胞中的多胺转运以及从海马切片中释放精子的多胺转运，从而检查了多胺（精子和精子）的脑。发现突触细胞和神经胶质细胞中存在膜电位依赖性的多胺传输系统，而突触蔬菜中存在质子梯度依赖性的多胺传输系统。发现精子在突触蔬菜中积累，并使用高浓度的KCL通过二极化释放出从大鼠海马切片中释放出来。多胺，尤其是精子可以用作大脑中的神经调节剂。

项目成果

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Yoshida, M. 等人：“多胺通过抑制开放阅读框中的琥珀终止密码子来增强 RNA 聚合酶 σ^<38> 亚基的合成”J.Biol.Chem.. 277. 37139-37146 (2002)

Williams, K. et al.: "Pharmacology of σ2 glutamate receptors : Effect of pentamidine and protons"J.Pharmacol.Exp.Ther.. 305. 740-748 (2003)

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Nishimura, K. et al.: "Essential role of S-adenosylmethionine decarboxylase in mouse embryonic development."Genes Cells. 7. 41-47 (2002)

Nishimura, K. 等人：“S-腺苷甲硫氨酸脱羧酶在小鼠胚胎发育中的重要作用。”基因细胞。