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2007 Fiscal Year Final Research Report Summary

On the Possible Control of Allergic Inflammation based on Molecular Mechanism of Serotonin Synthesizing Enzyme

Research Project

Project/Area Number 16591872
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionTeikyo University of Science & Technology

Principal Investigator

HASEGAWA Hiroyuki  Teikyo University of Science & Technology, Biosciences, Professor (10092983)

Co-Investigator(Kenkyū-buntansha) NAKANISHI Nobuo  Meikai University, Dentistry, Instructor (20118574)
SAWABE Keiko  Teikyo University of Science and Technology, Biotechnology, Research Center, Part-time Researcher (10399008)
Project Period (FY) 2004 – 2007
KeywordsTryptopha hydroxylase / Serotonin biosynthesis / Enzyme regulation by phosphorylation / Ubiquitination / Proteasomes / Site-directed mutagenesis / RBL2H3
Research Abstract

Tryptophan hydroxykase, the rate limiting enzyme in serotonin biosynthesis, exists in two isoforms. In 2003, TPH2 gene was identified and the gene product was named TPH2 while the long known gene product was newly referred to TPH1. The level of tryptophan hydroxylase in cells of RBL2H3, a mast-cell line, was shown to be under very rapid molecular turnover driven by the Ubiquitin-Proteasome system in the cell. The degradation process is triggered by protein phosphorylation of the enzyme. The phosphorylation site(s) responsible for triggering is(are) not known. In this study, three major progresses were achieved: 1)Polyclonal mono-specific antibodies were raised against TPH1 and TPH2. By the use of these antibodies, dominant distribution of TPH2 in the brain and TPH1 in the peripheral tissues were confirmed. However, we found that TPH1 was also detected in the brain and TPH2 in the non-neural cells in the periphery. Further, we located TPH1 in the intestinal absorption epithelia which had been believed to lack in the hydroxylase. 2) We reported previously that in vitro immune stimulation to RBL2H3 cells with IgE-antigen complex, triggered a rapid and prominent induction of TPH1. In this study, it was demonstrated that NF-kB pathway was involved in the signal transduction of the TPH1-induction. 3) Variant TPH1 vectors were developed of which 3 serine residues (S58, S260, and S443) on the protein surface were replaced with either alanine or glutamic acid by means of site-directed mutagenesis. The variants were all active when transected to HeLa cells, a cell line lack in TPH. Currently, the variants are under examination whether they are susceptible to the molecular degradation in RBL2H3 cells which are furnished with the all the required Ubiquitin-Proteasome system specific to the wild type TPH1.

  • Research Products

    (18 results)

All 2008 2007 2006 2005 2003 Other

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (3 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Role of a Serotonin Precursor in Development of Gut Microvilli2008

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

      Am J Pathol 172

      Pages: 333-44

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Role of a Serotonin Precursor in Development of Gut Microvilli.2008

    • Author(s)
      Nakamura, K., T. Sato, A. Ohashi, H. Tsurui, H. Hasegawa
    • Journal Title

      Am J Pathol 172(2)

      Pages: 333-44

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A new gain-of-function allele in chimpanzee tryptophan hydroxylase 2 and the comparison of its enzyme activity with that in humans and rats2007

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

      Neurosci Lett 412

      Pages: 195-200

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Developmental role of tryptophan hydroxylase in the nervous system2007

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

      Mol Neurobiol 35

      Pages: 45-54

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] A new gain-of-function allele in chimpanzee tryptophan hydroxylase 2 and the comparison of its enzyme activity with that in humans and rats.2007

    • Author(s)
      Hong, K. W., Y. Sugawara, H. Hasegawa, I. Hayasaka, R. Hashimoto, S. Ito, M. Inoue-Murayama
    • Journal Title

      Neurosci Lett 412(3)

      Pages: 195-200

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Developmental role of tryptophan hydroxylase in the nervous system.2007

    • Author(s)
      Nakamura, K., H. Hasegawa
    • Journal Title

      Mol Neurobiol 35(1)

      Pages: 45-54

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Requirement of tryptophan hydroxylase during development for maturation of sensorimotor gating2006

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

      J Mol Biol 363

      Pages: 345-54

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Late developmental stage-specific role of tryptophan hydroxylase 1 in brain serotonin levels2006

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

      J Neurosci 26

      Pages: 530-4

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Requirement of tryptophan hydroxylase during development for maturation of sensorimotor gating.2006

    • Author(s)
      Nakamura, K., Y. Koyama, K. Takahashi, H. Tsurui, Y. Xiu, M. Ohtsuji, Q. S. Lin, Y. Sugawara, K. Sawabe, A. Ohashi, T. Ohnuma, H. Arai, H. Nishimura, H. Hasegawa, S. Hirose
    • Journal Title

      J Mol Biol 363(2)

      Pages: 345-54

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Late developmental stage-specific role of tryptophan hydroxylase 1 in brain serotonin levels.2006

    • Author(s)
      Nakamura, K., Y. Sugawara, K. Sawabe, A. Ohashi, H. Tsurui, Y. Xiu, M. Ohtsuji, Q. S. Lin, H. Nishimura, H. Hasegawa, S. Hirose
    • Journal Title

      J Neurosci 26(2)

      Pages: 530-34

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Distinctive iron requirement of tryptophan 5-monooxygenase:TPH1 requires dissociable ferrous iron2005

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

      Biochem Biophys Res Commun 338

      Pages: 277-84

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Distinctive iron requirement of tryptophan 5-monooxygenase : TPH1 requires dissociable ferrous iron.2005

    • Author(s)
      Hasegawa, H., A. Ichiyama
    • Journal Title

      Biochem Biophys Res Commun 338(1)

      Pages: 277-84

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Immunohistochemical and enzymological detection of tryptophan hydroxylase in villus epithelium of intestinal mucosa2007

    • Author(s)
      Ohashi, A., et. al.
    • Organizer
      26th International winter-workshop clinical, chemical, & biochemical aspects of pteridines
    • Place of Presentation
      St.Christoph,Austria
    • Year and Date
      2007-03-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Immunohistochemical and enzymological detection of tryptophan hydroxylase in villus epithelium of intestinal mucosa.2007

    • Author(s)
      Ohashi, A., K. Nakamura, T. Sato, H. Hasegawa.
    • Organizer
      26th International winter-workshop clinical, chemical, & biochemical aspects of pteridines
    • Place of Presentation
      St. Christoph/Arlberg, Austria
    • Year and Date
      2007-03-06
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 大橋晶子,中村和裕,佐藤拓,長谷川宏幸.トリプトファン水酸化酵素(TPH)の2つのアイソファームTPH1,TPH2に特異的な抗体の作成と免疫組織化学による小腸上皮組織のTPHの検出2006

    • Author(s)
      大橋 晶子, 他
    • Organizer
      第10回活性アミンに関するワークショップ
    • Place of Presentation
      東京
    • Year and Date
      2006-08-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Proceedings of 13th International Symposium on Chemistry & Biology of Pteridines & Folates2007

    • Author(s)
      Hasegawa, H., et. al.
    • Total Pages
      18/607(256-273)
    • Publisher
      SPS Publication,Germany
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Pterines, Folates and Neurotransmitters in Molecular Medicine2003

    • Author(s)
      Sawabe, K., et. al.
    • Total Pages
      7/xxx(41-4
    • Publisher
      SPS Publications,Germany
    • Description
      「研究成果報告書概要(和文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.ntu.ac.jp/dept/bio/btrc/h/hasegawa/30.html

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Published: 2010-02-04  

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