2007 Fiscal Year Final Research Report Summary
On the Possible Control of Allergic Inflammation based on Molecular Mechanism of Serotonin Synthesizing Enzyme
| Project/Area Number |
16591872
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Teikyo University of Science & Technology |
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Principal Investigator |
HASEGAWA Hiroyuki Teikyo University of Science & Technology, Biosciences, Professor (10092983)
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| 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)
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| Project Period (FY) |
2004 – 2007
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| Keywords | Tryptopha hydroxylase / Serotonin biosynthesis / Enzyme regulation by phosphorylation / Ubiquitination / Proteasomes / Site-directed mutagenesis / RBL2H3 |
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| 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.
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[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
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Journal Title
J Mol Biol 363(2)
Pages: 345-54
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
J Neurosci 26(2)
Pages: 530-34
Description
「研究成果報告書概要(欧文)」より
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