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1996 Fiscal Year Final Research Report Summary

Signal transduction system in osteoclasts through tetrahydrobiopterin-mediated production of NO and cGMP.

Research Project

Project/Area Number 07672026
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionMeikai University

Principal Investigator

KATOH Setsuko  Meikai University, School of Dentistry, Professor, 歯学部, 教授 (50049376)

Co-Investigator(Kenkyū-buntansha) FUJIMOTO Kengo  School of Dentistry, Assistant, 歯学部, 助手 (90286013)
Project Period (FY) 1995 – 1996
KeywordsOsteoclasts / Nitric oxide / Tetrahydrobioptein / cGMP / Signal transduction
Research Abstract

Nitric oxide (NO) inhibits osteoclast activity, but the signal transduction mechanism is not understood. cGMP and cGMP-dependent protein kinase signling pathway mediate several physiologic effects of NO possiblly including bone resorption. NO synthase (NOS) was recently shown to require tetrahydrobiopter in (BH4) as an natural cofactor in its activity. Thus it is of great interest to know the regulation mechanism of bone resorption by BH4 content in the osteoclast through activation of NOS and the resulted formations of NO and cGMP.However, nothing is known about the ability of BH4 synthesis in osteoclasts. Therefore, we studied the occurence of BH4-synthesyzing enzymes and BH4 content in the osteoclaset, cDNA of sepiapterin reductase, an enzyme involved in the last step of the biosynthetic pathway of BH4, was amplified by RT-PCR method and expressed by E.coli. The protein which shows the enzyme activity has been obtained and purified to homogeneity. And the polyclonal antibody was prepared against the protein. These are usefull for detecting the level and localization of BH4-synthesis in the osteoclasts. We could isolated cell mass containing more than 95% osteoclasts from bonemarrows of rabbit thigh bones with great difficulty as the enough amount to assay BH4 or NO content in the cell. And contents of BH4 and NO detected per 10^5cells were quite significant. Thus we have found that the osteoclast has the ability for BH4 synthesis and we could established a kit for analysis the relation between the formation of BH4, NO,and cGMP,and osteoclasis.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] 加藤節子: "Ca/Calmodulin-dependent protein kinase IIによるテトラヒドロビオプテリン生成酵素系のリン酸化反応" VITAMINS. 69(4). 271 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Setsuko Katoh: "Regulation of susceptibility of tetrahydrobiopter in generating enzymes." Zoological Science. 12. 49 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加藤節子: "ビオプテリン補酵素(モノアミン調節因子)合成系のリン酸化による調節機構" 歯科基礎医学会誌. 37. 213 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加藤節子: "テトラヒドロビオプテリン生合成酵素のCa2+依存性リン酸化におけるCALPAIN感受性" 生化学. 67(7). 711 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加藤節子: "開口分泌に関与する低分子量タンパク質のターゲットタンパクはGTPシクロヒドロラーゼ1と結合している." VITAMINS. 69(7). 401-403 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akira Ota: "Tetrahydrobiopter in biosynthesis enhanced by LPS stimulation in mur ine neuroblastoma cell line N1E-115." Journal of Neurochemistry. 67(6). 2540-2548 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sumiko Negishi: "Yellow marking and pteridine contents in the integment of albino Armadillium vulgare." Pigment Cell Res.9. 35-41 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kengo Fujimoto: "Modulation of tetrahydrobiopter in generating enzymes by limited proteolysis with CANP." Zoological Science. 13(DEC). 44 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加藤節子: "テトラヒドロビオプテリン生成酵素系のCa2+による分解制御." VITAMINS. 70(4). 179 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 藤本健吾: "テトラヒドロビオプテリン生成酵素のカルパインによる機能修飾." 生化学. 68(7). 914 (1996)

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      「研究成果報告書概要(和文)」より
  • [Publications] 加藤節子: "一酸化窒素合成酵素(NOS)のプテリン補酵素結合部位." VITAMINS. 70(7). 345-347 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 藤本健吾: "Ca2+/カルモジュリン依存性プロティンキナーゼ11とCa2+依存性プロテアーゼによるビオプテリン補酵素調節." 歯科基礎医学会誌. 38. 487 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 藤本健吾: "ビオプテリン補酵素生成系酵素の遺伝子座." VITAMINS. 71(2). 103-106 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katoh, S., Yamamoto, Y., and Takahashi, S.: "Phosphorylation of tetrahydrobiopter in-generating eyzymes by Ca/calmodulin-dependent protein kinase II." VITAMINS. 69 (4). 271 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katoh, S., Yamamoto, Y., and Takahashi, S.: "Regulation of susceptibility of tetrahydrobiopter in generating enzymes." Zoo.Science. 12 (DEC). 49 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katoh, S., Yamamoto, Y., and Takahashi, S.: "Control system of the production of biopterin cofactor for monoamine synthesis by phosphorylation." Jpn.J.Dent.Scien.37. 213 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katoh, S., Ichinose, H., Nagatsu, T., Yamamoto, Y., Takahashi, S.: "Sensitivity to CALPAIN of tetrahydrobiopter in generating enzyme phosphorylated by Ca-dependent protein kinases." SEIKAGAKU. 67 (7). 711 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katoh, S.: "The target protein of the low molecular G protein acting on the exocytosis is binding with GTP cychlohydrolase I." VITAMINS. 69 (7). 401-403 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ota, A., Yoshida, S., Nomura, T., Matsui, S., Hagino, Y., Umezawa, K., Katoh, S., and Nagatsu, T.: "Tetrahydrobiopterin biosynthesis enhanced by LPS stimulation in murine neuroblastoma cell line N1E-115." Journal of Neurochemistry. 69 (6). 2540-2548 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Negishi, S., Sueoka, T., Hasegawa Y., and Katoh, S.: "Yellow marking and pteridine contents in the integment of albino Armadillium vulgare." Pigment Cell Res.9. 35-41 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujimoto, K., Inaba, A., Tomomura, A., Haino, K., Yamamoto, Y., Takahashi, S., and Katoh, S.: "Modulation of tetrahydrobiopterin generating enzymes by limited proteolysis with CANP." Zool.Scien.13 (DEC). 44 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katoh, S., Fujimoto, K., Yamamoto, Y.and Takahashi, S: "Degradation of tetrahydrobiopterin-genarating enzymes controlled by Ca^<2+>." VITAMINS. 70 (4). 179 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujimoto, K., Inaba, A., Haino, K., Yamamoto, Y., Takahashi, S., and Katoh, S.: "Functional modification of tetrahydrobiopterin-generating enyzmes by CALPAIN." SEIKAGAKU. 68 (7). 914 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Katoh, S.: "Pterin binding site on nitric oxide synthase (NOS)." VITAMINS. 70 (7). 345-347 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujimoto, K., Inaba, A., Yamamoto, Y., Takahashi, S., and Katoh, S.: "Formation of biopterin cofactor is regulated by Ca^<2+>/calmodulin-depenmdent protein kinase II and Ca^<2+> -dependent protease." Jpn.J.Dent.Scien.38. 487 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujimoto, K., and Katoh, S.: "Gene locuses of enzymes involved in the formation of biopterin cofactor." VITAMINS. 71 (2). 103-106 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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