Molecular mechanism and physiological role of polyamine transport systems and NMDA receptors

多胺转运系统和NMDA受体的分子机制和生理作用

基本信息

  • 批准号:
    18590069
  • 负责人:
  • 金额:
    $ 2.57万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2006
  • 资助国家:
    日本
  • 起止时间:
    2006 至 2007
  • 项目状态:
    已结题

项目摘要

1. N-Methyl-D-aspartate(NMDA)receptors are involved in synaptic plasticity and may also play a role in seizure activity. Overactivation of these receptors can lead to neuronal cell death. Thus, NMDA receptors are potential targets for anticonvulsants and neuroprotective agents. We found that anthraquinone (AQ)- and anthracene (Ant)-tetraamines are potent NMDA channel blockers. The effects of both AQ- and Ant-tetraamines were reversible and voltage-dependent. Results of experiments using mutant NR1 and NR2B subunits of NMDA receptor identified residues that influence block by AQ- and Ant-tetraamines. The results indicate that the polyamine tail is crucial for block by AQ- and Ant-tetraamines. Residues in the outer vestibule of the NR1 subunit were more strongly involved in block by AQ- and Ant-tetraamines than residues in the corresponding region of NR2B.2. CadB, a cadaverine-lysine antiporter, is strongly involved in cell growth under acidic conditions in Escherichia coll. Amino acid residues involved in the activity of CadB were determined by site-directed mutagenesis of the gene. It was found that Cys370 is essential for the activity and was suggested that a hydrophilic cavity is formed by the transmembrane segments II, III, IV, VI, VII, X, XI and XII.3. We have looked for polyamine-preferential uptake proteins in S. cerevisiae. DUR3 catalyzed the uptake of polyamines together with urea, and SAM3 catalyzed the uptake of polyamines together with S-adenosylmethionine, glutamic acid and lysine. Polyamine uptake was greatly decreased in both DUR3- and SAM3-deficient cells. Polyamine stimulation of cell growth of a polyamine requiring mutant was completely inhibited by the disruption of both DUR3 and SAM3. The results indicate that DUR3 and SAM3 are major polyamine uptake proteins in yeast. It was found that DUR3, but not SAM3, was activated by phosphorylation by polyamine transport protein kinase 2.
1. n -甲基- d -天冬氨酸(NMDA)受体参与突触可塑性,也可能在癫痫发作活动中发挥作用。这些受体的过度激活可导致神经元细胞死亡。因此,NMDA受体是抗惊厥药和神经保护剂的潜在靶点。我们发现蒽醌(AQ)-和蒽(Ant)-四胺是有效的NMDA通道阻滞剂。AQ-和抗四胺的作用都是可逆的和电压依赖性的。实验结果表明,NMDA受体突变体NR1和NR2B亚基鉴定出影响AQ-和anti -四胺阻断的残基。结果表明,多胺尾部对AQ-和anti -四胺的阻断至关重要。NR1亚基外前庭的残基比NR2B.2的相应区域的残基更强烈地参与AQ-和anti -四胺的阻断。CadB是一种尸胺赖氨酸反转运蛋白,在大肠杆菌酸性条件下强烈参与细胞生长。参与CadB活性的氨基酸残基是通过基因的定点诱变确定的。研究发现Cys370对活性至关重要,并认为跨膜段II、III、IV、VI、VII、X、XI和xii形成亲水性空腔。我们在酿酒酵母中寻找多胺优先摄取蛋白。DUR3与尿素一起催化多胺的摄取,SAM3与s -腺苷蛋氨酸、谷氨酸和赖氨酸一起催化多胺的摄取。在DUR3-和sam3缺陷细胞中,多胺摄取都大大减少。多胺对多胺需要突变体细胞生长的刺激作用被DUR3和SAM3的破坏完全抑制。结果表明,DUR3和SAM3是酵母主要的多胺摄取蛋白。发现DUR3被多胺转运蛋白激酶2磷酸化激活,而SAM3不被激活。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Docosahexaenoic acid inhibits growth of mouse mammary cancer cells by interfering with p27/kipl, Cdk2, ERK1/ERK2 and retinoblastoma phosphorylation.
二十二碳六烯酸通过干扰 p27/kipl、Cdk2、ERK1/ERK2 和视网膜母细胞瘤磷酸化来抑制小鼠乳腺癌细胞的生长。
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Khan;N;A;et al.
  • 通讯作者:
    et al.
Polyamine Uptake by DUR3 and SAM3 in Saccharomyces cerevisiae*
  • DOI:
    10.1074/jbc.m611105200
  • 发表时间:
    2007-03
  • 期刊:
  • 影响因子:
    4.8
  • 作者:
    T. Uemura;K. Kashiwagi;K. Igarashi
  • 通讯作者:
    T. Uemura;K. Kashiwagi;K. Igarashi
Polyamines in renal failure : Review article
肾衰竭中的多胺:评论文章
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Igarashi;K;et al.
  • 通讯作者:
    et al.
Decrease in polyamines with aging and their ingestion from food and drink
  • DOI:
    10.1093/jb/mvj003
  • 发表时间:
    2006-01-01
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    Nishimura, K;Shiina, R;Igarashi, K
  • 通讯作者:
    Igarashi, K
Anthraquinone polyamines : novel channel blockers on N-methyl-D-aspartate receptors
蒽醌多胺:N-甲基-D-天冬氨酸受体的新型通道阻滞剂
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kashiwagi;K.;et. al.
  • 通讯作者:
    et. al.
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KASHIWAGI Keiko其他文献

Enhanced biofilm formation and cell viability by polyamines through stimulation of response regulators UvrY and CpxR in the two-component signal transducing systems and ribosome recycling factor
多胺通过刺激双组分信号转导系统中的反应调节剂 UvrY 和 CpxR 以及核糖体循环因子增强生物膜形成和细胞活力
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    0
  • 作者:
    SAKAMOTO Akihiko;TERUI Yusuke;YAMAMOTO Taku;KASAHARA Takuma;NAKAMURA Mizuho;TOMITORI Hideyuki;YAMAMOTO Kaneyoshi;MICHAEL Anthony J.;IGARASHI Kazuei;KASHIWAGI Keiko
  • 通讯作者:
    KASHIWAGI Keiko

KASHIWAGI Keiko的其他文献

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{{ truncateString('KASHIWAGI Keiko', 18)}}的其他基金

Physiological role of polyamines and regulation of their cellular contents
多胺的生理作用及其细胞内容物的调节
  • 批准号:
    23590088
  • 财政年份:
    2011
  • 资助金额:
    $ 2.57万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Structure and functions of polyamine transport proteins and NMDA receptors
多胺转运蛋白和 NMDA 受体的结构和功能
  • 批准号:
    20590066
  • 财政年份:
    2008
  • 资助金额:
    $ 2.57万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Structure and function of polyamine transport systems and NMDA receptors
多胺转运系统和 NMDA 受体的结构和功能
  • 批准号:
    16590042
  • 财政年份:
    2004
  • 资助金额:
    $ 2.57万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Cultural and Developmental Perspectives on Social Change and Family, Self and Gender
社会变革与家庭、自我和性别的文化和发展视角
  • 批准号:
    15330143
  • 财政年份:
    2003
  • 资助金额:
    $ 2.57万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Characterization of polyamine transport systems and modulation of NMDA receptor by polyamines
多胺转运系统的表征和多胺对 NMDA 受体的调节
  • 批准号:
    14572052
  • 财政年份:
    2002
  • 资助金额:
    $ 2.57万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Culture Psychological Research on Family and Individual Development in changing society
变革社会中家庭与个人发展的文化心理学研究
  • 批准号:
    12410038
  • 财政年份:
    2000
  • 资助金额:
    $ 2.57万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Characteristics of polyamine transport and regulation of its gene expression
多胺转运特性及其基因表达调控
  • 批准号:
    09672214
  • 财政年份:
    1997
  • 资助金额:
    $ 2.57万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Japan-U.S.study on self development and socio-cultural context in adolescence
日美青少年自我发展与社会文化背景研究
  • 批准号:
    07044011
  • 财政年份:
    1995
  • 资助金额:
    $ 2.57万
  • 项目类别:
    Grant-in-Aid for international Scientific Research
Regulation of polyamine contents in cells
细胞内多胺含量的调节
  • 批准号:
    07680645
  • 财政年份:
    1995
  • 资助金额:
    $ 2.57万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Japan-U.S.study on self development and socio-cultural context adolescence
日美青少年自我发展与社会文化背景研究
  • 批准号:
    06301016
  • 财政年份:
    1994
  • 资助金额:
    $ 2.57万
  • 项目类别:
    Grant-in-Aid for Co-operative Research (A)

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抗衰老因子亚精胺保护肾脏和全身
  • 批准号:
    23K07675
  • 财政年份:
    2023
  • 资助金额:
    $ 2.57万
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亚精胺作为结肠炎的新疗法和结肠炎相关癌的化学预防
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    10379376
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亚精胺作为结肠炎的新疗法和结肠炎相关癌的化学预防
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The study for mechanism of zebrafish skin pattern pattern formation by spermidine
亚精胺对斑马鱼皮肤花纹形成机制的研究
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膳食亚精胺和精胺摄入可增强啮齿动物短肠综合征模型中的肠道屏障并防止肝细胞脂滴沉积
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    15H02776
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蛋白脂质体研究亚精胺输出体的底物转运机制
  • 批准号:
    21880011
  • 财政年份:
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亚精胺赋予非生物胁迫耐受性的功能分析
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  • 资助金额:
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