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Regulation of cell growth and brain function by polyamines

Research Project

Project/Area Number 16390018
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionChiba University

Principal Investigator

IGARASHI Kazuei  Chiba University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究院, 教授 (60089597)

Co-Investigator(Kenkyū-buntansha) KASHIWAGI Keiko  Chiba University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究院, 助教授 (80169424)
NISHIMURA Kazuhiro  Chiba University, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究院, 講師 (60302569)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥10,800,000 (Direct Cost: ¥10,800,000)
KeywordsPolyamine / 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
Research Abstract

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

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (22 results)

All 2005 2004

All Journal Article (22 results)

  • [Journal Article] Characteristics of the polyamine transporter TPO1 and regulation of its activity and cellular localization by phosphorylation2005

    • Author(s)
      Uemura, T., et al.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 9646-9652

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Excretion of putrescine and spermidine by the protein encoded by YKL174c(TPO5) in Saccharomyces cerevisiae2005

    • Author(s)
      Tachihara, K., et al.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 12367-12462

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polyamine oxidase and acrolein as novel biochemical markers for diagnosis of cerevral stroke2005

    • Author(s)
      Tomitori, H., et al.
    • Journal Title

      Stroke 36

      Pages: 2609-2613

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polyamine transport by mammalian cells and mitochondria : Role of antizyme and glycosaminoglycans2005

    • Author(s)
      Hoshino, K., et al.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 42801-42808

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characteristics of the polyamine transporter TPO1 and regulation of its activity and cellular, localization by phosphorylation.2005

    • Author(s)
      Uemura, T. et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 9646-9652

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Excretion of putrescine and spermidine by the protein encoded by YKL174c (TPO5) in Saccharomyces cerevisiae.2005

    • Author(s)
      Tachihara, K. et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 12637-12642

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polyamine oxidase and acrolein as novel biochemical markers for diagnosis of cerebral stroke.2005

    • Author(s)
      Tomitori, H. et al.
    • Journal Title

      Stroke 36

      Pages: 2609-2613

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polyamine transport by mammalian cells and mitochondria : Role of antizyme and glyposaminoglycans.2005

    • Author(s)
      Hoshino, K. et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 42801-42808

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Independent roles of eIF5A and polyamines in cell proliferation2005

    • Author(s)
      Nishimura, K. et al.
    • Journal Title

      Biochem.J. 385

      Pages: 779-785

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Characteristics of the polyamine transporter TPO1 and regulation of its activity and cellular localization by phosphorylation2005

    • Author(s)
      Uemura, T. et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 9646-9652

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Excretion of putrescine and spermidine by the protein encoded by YKL174c (TPO5) in Saccharomyces cerevisiae2005

    • Author(s)
      Tachihara, K. et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 12637-12642

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Modulation of blood coagulation and fibrinolysis by polyamines in the presence of glycosaminoglycans2005

    • Author(s)
      Homma, R. et al.
    • Journal Title

      Int.J.Biochem.Cell Biol. 37

      Pages: 1911-1920

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Polyamine oxidase and acrolein as novel biochemical markers for diagnosis of cerebral stroke2005

    • Author(s)
      Tomitori, H. et al.
    • Journal Title

      Stroke 36

      Pages: 2609-2613

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Polyamine transport by mammalian cells and mitochondria : Role of antizyme and glycosaminoglycans2005

    • Author(s)
      Hoshino, K. et al.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 42801-42808

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Anthraquinone polyamines : Novel channel blockers to study NMDA receptors2004

    • Author(s)
      Kashiwagi, K., et al.
    • Journal Title

      J. Pharmacol. EXP. Ther. 309

      Pages: 884-893

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A unifying model for the role of polyamines in bacterial cell growth : the polyamine modulon2004

    • Author(s)
      Yoshida, M., et al.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 46008-46013

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anthraquinone polyamines : Novel channel blockers to study NMDA receptors.2004

    • Author(s)
      Kashiwagi, K. et al.
    • Journal Title

      J.Pharmacol.Exp.Ther. 309

      Pages: 884-893

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] A unifying model for the role of polyamines in bacterial cell growth : the polyamine modulon.2004

    • Author(s)
      Yoshida, M. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 46008-46013

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Excretion and uptake of cadaverine by CadB and its physiological functions in Escherichia coli.2004

    • Author(s)
      Soksawatmaekhin, W. et al.
    • Journal Title

      Mol.Microbiol. 51

      Pages: 1401-1402

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Uptake of GABA and putrescine by UGA4 on the vacuolar membrane in Saccharomyces cerevisiae.2004

    • Author(s)
      Uemura T., et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 315

      Pages: 1082-1087

    • Related Report
      2004 Annual Research Report
  • [Journal Article] TATA-binding protein-associated factor 7 regulates polyamine transport activity and polyamine analogue-induced apoptosis.2004

    • Author(s)
      Fukuchi, J. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 29921-29929

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Structural and functional relationship among diamines in terms of inhibition of cell growth.2004

    • Author(s)
      Higashi, K. et al.
    • Journal Title

      J.Biochem. 136

      Pages: 533-539

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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