Regulation of cell growth and brain function by polyamines

多胺调节细胞生长和脑功能

• 批准号: 16390018
• 负责人: IGARASHI Kazuei
• 金额: $ 9.66万
• 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390018/
• 关键词: Polyamine; Modulon; Spermidine; Spermine; NMDA receptor; Anthraquinone spermidine; Acrolein; Stroke; eIF5A; チトクロムc; ポリアミン輸送; 蛋白質合成; 細胞増殖; チャネルブロッカー; AQポリアミン

1. We have reported previously that the synthesis of specific proteins such as OppA, Cya and RpoS (σ^<38>), which are important for cell growth, is stimulated by polyamines at the level of translation in E.coli. We found that the synthesis of FecI and Fis was also stimulated by polyamines at the level of translation. The FecI and Fis enhance expression of mRNAs that are involved in iron uptake and energy metabolism, and of rRNA and some tRNAs. The Shine-Dalgarno (SD) sequence of their mRNAs was not located at the usual position. When the 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 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. The effects of various anthraquinone polyamines (AQP) were studied at NMDA receptors expressed in Xenopus l … More aevis oocytes. All AQP derivatives inhibited responses of NR1/NR2 receptors in oocytes voltage-clamped at -70mV, with IC_<50> values between 4 and 22μM. The block was strongly voltage-dependent. AQ spermidine (AQ34) inhibited responses of NR1/NR2 receptors but did not inhibit responses of AMPA receptors indicating that AQ34 is preferential NMDA antagonists. Results of experiments using mutant NR1 and NR2 subunits identified residues that influence block by AQ34. These residues are located in the outer vestibule at the selectivity filter/narrowest constriction of the channel and in the inner vestibule below the level of the selectivity filter.3. The levels of acetylpolyamine oxidase (AcPAO), spermine oxidase (SMO), and acrolein were significantly increased in the plasma of stroke patients. The size of stroke was nearly parallel with the multiplied value of acrolein and total polyamine oxidase (AcPAO plus SMO). After the onset of stroke, an increase in AcPAO first occurred, followed by increased level of SMO and finally acrolein. In 1 case, an increase in AcPAO and SMO preceded focal damage as detected by MRI or CT. Furthermore, stroke was confirmed by MRI in a number of mildly symptomatic patients (11 cases) who had increased levels of total polyamine oxidase and acrolein. The results indicate that AcPAO, SMO, and acrolein are good markers of stroke. Less

1. 我们以前报道过，在大肠杆菌中，多胺在翻译水平上刺激了对细胞生长重要的特定蛋白质的合成，如OppA、Cya和RpoS （σ^<38>）。我们发现多胺在翻译水平上也刺激了FecI和Fis的合成。FecI和Fis增强了参与铁摄取和能量代谢的mrna以及rRNA和一些trna的表达。他们的mrna的Shine-Dalgarno （SD）序列不在通常的位置。当在这些mrna的正常位置产生SD序列时，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SD序列。我们提出，在翻译水平上多胺增强表达的一组基因被称为“多胺调节”。研究了各种蒽醌多胺（AQP）对爪蟾卵母细胞表达的NMDA受体的影响。所有AQP衍生物均抑制NR1/NR2受体在-70mV电压箝位下的卵母细胞的反应，在4 ~ 22μM范围内IC_<50>。该块与电压密切相关。AQ34可抑制NR1/NR2受体的反应，但对AMPA受体的反应无抑制作用，提示AQ34是优先的NMDA拮抗剂。使用突变体NR1和NR2亚基的实验结果确定了影响AQ34阻断的残基。这些残留物位于选择性过滤器/通道最窄处的外前庭和低于选择性过滤器水平的内前庭。脑卒中患者血浆乙酰多胺氧化酶（AcPAO）、精胺氧化酶（SMO）、丙烯醛水平均显著升高。脑卒中的大小与丙烯醛和总多胺氧化酶（AcPAO + SMO）的乘积值几乎平行。卒中发生后，AcPAO首先升高，其次是SMO水平升高，最后是丙烯醛水平升高。在1例患者中，MRI或CT检测到AcPAO和SMO的升高先于局灶性损伤。此外，在一些轻度症状的患者（11例）中，总多胺氧化酶和丙烯醛水平升高，MRI证实中风。结果表明AcPAO、SMO和丙烯醛是较好的脑卒中标志物。少

项目成果

Structural and functional relationship among diamines in terms of inhibition of cell growth

• DOI: 10.1093/jb/mvh150
• 发表时间: 2004-10-01
• 期刊: JOURNAL OF BIOCHEMISTRY
• 影响因子: 2.7
• 作者: Higashi, K;Yoshida, K;Igarashi, K
• 通讯作者: Igarashi, K

Polyamine transport by mammalian cells and mitochondria - Role of antizyme and glycosaminoglycans

• DOI: 10.1074/jbc.m505445200
• 发表时间: 2005-12-30
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Hoshino, K;Momiyama, E;Igarashi, K
• 通讯作者: Igarashi, K

Uptake of GABA and putrescine by UGA4 on the vacuolar membrane in Saccharomyces cerevisiae.

酿酒酵母液泡膜上的 UGA4 对 GABA 和腐胺的摄取。

• 发表时间: 2004
• 期刊: Biochem.Biophys.Res.Commun. 315
• 作者: Uemura T.;et al.
• 通讯作者: et al.

A unifying model for the role of polyamines in bacterial cell growth : the polyamine modulon

多胺在细菌细胞生长中作用的统一模型：多胺模量

• 发表时间: 2004
• 期刊: J. Biol. Chem. 279
• 作者: Yoshida;M.;et al.
• 通讯作者: et al.

Excretion and uptake of cadaverine by CadB and its physiological functions in Escherichia coli

• DOI: 10.1046/j.1365-2958.2003.03913.x
• 发表时间: 2004-03-01
• 期刊: MOLECULAR MICROBIOLOGY
• 影响因子: 3.6
• 作者: Soksawatmaekhin, W;Kuraishi, A;Igarashi, K
• 通讯作者: Igarashi, K