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

Research Project

Project/Area Number 14370739
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)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥10,100,000 (Direct Cost: ¥10,100,000)
KeywordsPolyamine / 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
Research Abstract

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.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kashiwagi, K. et al.: "Channel blockers acting at N-methyl-D-aspartate receptors : Differential effects of mutations in the vestibule and ion channel pore"Mol.Pharmacol.. 61. 533-545 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kashiwagi, K. et al.: "The ATPase activity and the functional domain of PotA, a component of the spermidine-preferential uptake system in Escherichia coli"J.Biol.Chem.. 277. 24212-24219 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshida, M. et al.: "Polyamines enhance synthesis of the RNA polymerase σ^<38> subunit by suppression of an amber termination codon in the open reading frame"J.Biol.Chem.. 277. 37139-37146 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masuko, T. et al.: "Polyamine transport, accumulation, and release in brain"J.Neurochem.. 84. 610-617 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sakata, K. et al.: "Increase in putrescine, amine oxidase and acrolein in plasma of renal failure patients"Biochem.Biophys.Res.Commun.. 305. 143-149 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishimura, K. et al.: "Essential role of S-adenosylmethionine decarboxylase in mouse embryonic development."Genes Cells. 7. 41-47 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kashiwagi, K. et al.: "Channel blockers acting at N-methyl-D-aspartate receptors : Differential effects of mutations in the vestibule and ion channel pore."Mol.Pharmacol.. 61. 533-545 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kashiwagi, K. et al.: "The ATPase activity and the functional domain of PotA, a component of the spermidine-preferential uptake system in Escherichia coli."J.Biol.Chem.. 277. 24212-24219 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshida, M. et al.: "Polyamines enhance synthesis of the RNA polymerase σ^<38> by suppression of an amber termination codon in the open reading frame."J.Biol.Chem.. 277. 37139-37146 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masuko, T. et al.: "Polyamine transport, accumulation, and release in brain."J.Neurochem.. 84. 610-617 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sakata, K. et al.: "Increase in putrescine, amine oxidase and acrolein in plasma of renal failure patients."Biochem.Biophys.Res.Commun.. 305. 143-149 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masuko, T. et al.: "Polyamine transport, accumulation, and release in brain"J.Neurochem.. 84. 610-617 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Williams, K. et al.: "Pharmacology of σ2 glutamate receptors : Effect of pentamidine and protons"J.Pharmacol.Exp.Ther.. 305. 740-748 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakata, K. et al.: "Acrolein produced from polyamines as one of the uremic toxins"Biochem.Soc.Trans.. 31. 371-374 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakata, K. et al.: "Increase in putrescine, amine oxidase, and acrolein in plasma of renal failure patients"Biochem.Biophys.Res.Commun.. 305. 143-149 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Low, C.-H.et al.: "Molecular determinants of proton-sensitive N-methyl-D-aspartate receptor gating"Mol.Pharmacol.. 63. 1212-1222 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Soksawatmaekhin, W. et al.: "Excretion and uptake of cadaverine by CadB and its physiological functions in Escherichia coli"Mol.Microbiol.. 51(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishimura, K. et al.: "Essential role of S-adenosylmethionine decarboxylase in mouse embryonic development"Genes Cells. 7. 41-47 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kashiwagi, K. et al.: "Channel blockers acting N-methyl-D-aspartate receptors : Differential effects of mutations in the vestibule and ion channel pore"Mol. Pharmacol.. 61. 533-545 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishimura, K. et al.: "Inhibition of cell growth through inactivation of eIF5A by deoxyspergualin"Biochem. J.. 363. 761-768 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kashiwagi, K. et al.: "The ATPase activity and the functional domain of PotA, a component of the spermidine-preferential uptake system in Escherichia coli"J. Biol. Chem.. 277. 24212-24219 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida, M. et al.: "Polyamines enhance synthesis of the RNA polymerase σ^<38> by suppression of an amber termination codon in the open reading frame"J. Biol. Chem.. 277. 37139-37146 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Raj, V.S.et al.: "Decrease in cell viability in an RMF, σ^<38> and OmpC triple mutant of Escherichia coli"Biochem. Biophys. Res. Commun.. 299. 252-257 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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