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Basic research in the connection of the cause of development of symptoms of diabetes and its complication

Research Project

Project/Area Number 10470531
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionMiyazaki Medical College

Principal Investigator

YAMAGUCHI Tadatoshi  Miyazaki Medical College, Dept of Hygiene, Ass. Prof., 医学部, 助教授 (80037598)

Co-Investigator(Kenkyū-buntansha) NOMURA Hajime  Miyazaki Medical College, Dept of Laboratory Medicine, Asist. Prof., 医学部, 助手 (80253839)
KASHIGE Nobuhiro  Fukuoka Univ., Faculty of Pharmaceutical Sciences, Asist. Prof., 薬学部, 助手 (80185751)
渡邊 健治 (渡邊 建治)  福岡大学, 薬学部, 教授 (40078689)
Project Period (FY) 1998 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsdihydropyrazine / DNA strand breakage / dihydrodiazepine / carbon-centered radical diabetes / diabetes / cultured cell / apoptosis / carbon-centeral radical / dihydropyrazime / DNA strand-breaKage / carbom-centered radical / Diabetes / DNA Strand-breakage / carbonーcentered radical / tetra azadecalin / D-glucosamine / DNA strand-breakage
Research Abstract

Elucidation of the mechanism of DNA strand-breakage by D-glucosamine, was attempted to clear. Then we aimed at applying the enlightened results for diabetic prevention and medical treatment. It is hitherto cleared that dihydrofructosazine which was derived from D-glucosamine, has a DNA strand-breakage activity. Thus, dihydropyrazines (DHPs), similar structure to dihydrofructosazine, were synthesized and recognized to reveal the activity. Some remarkable properties of DHPs have been revealed as shown in bellows.
1. DNA strand-breakage activity
2. Generation of hydroxyl and carbon-centered radicals
3. Noble chemical reaction
4. Nucleotide sequence specificity in DNA cleavage
Further, certain new facts are beginning to become apparent. That is to say, the autoradiogram of ^<14>C-labeled DHP showed that high uptake of ^<14>C-labeled DHP was observed in the spinal cord and also the brain. The effects of DHPs on cellular viability by culture assay of several cell lines, were examined. Cell morphological changes and the induction of apoptosis-related proteins were detected.
If the presence and the production of DHPs in vitro were exhibited, the connection of DHPs with certain diseases will be elucidated in future.

Report

(5 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] T.Yamaguchi et al.: "A Carbon-centered Radical as a Reaction Species in the DNA strand-Breakage by D-Glucoeamine"Biol. Pharm. Bull.. 21. 205-209 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Yamaguchi et al.: "Generation of Free Radicals from Dihydropyrazines with DNA strand-Breakage Activity"Tetrahedron Lett.. 39. 8311-8312 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Hiraku et al.: "Oxidative DNA Damage Induced by Aminoacetone, an Amino acid Metabolite"Archives of Biochemistry and Biophysics. 365. 62-70 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Yamaguchi et al.: "Producto from a Novel Reaction of Dihydropyrazines with Vichinaldiamine"Heterocycles. 51. 2305-2309 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Yamaguchi et al.: "A Diamine-Exchange Reaction of Dihydropyrazines"Heterocycles. 53. 1677-1680 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N.Kashige et al.: "Nucleotide Sequence Specificity in DNA Cleavage caused by Dihydropyrazines, a New Type of DNA Strand-cleaving Agent"Biol. Pharm. Bull.. 23. 1281-1286 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Yamaguchi et al.: "Reaction of 2,3-butanedione with propylenediamine Observed by 1H-NMR Spectroscopy"Heterocycles. 57. 11-16 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Yamaguchi et al.: "New Compounds Derived from Dihydropyrazines Having DNA strand-Breakage Activity"Tetrahedron. 55. 675-686 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamaguchi, T., Kashige, N., Matsumoto, S., Satoh, K., Yasuda, M. and Watanabe, K.: "A Carbon-Centered Radical as a Reaction Species in the DNA Strand-Breakage by D-Glucosamine"Biol. Pharm. Bull.. 21. 205-209 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamaguchi, T., Matsumoto, S. and Watanabe, K.: "Generation of Free Radicals from Dihydropyrazines with DNA Strand-Breakage Activity"Tetrahedron Lett.. 39. 8311-8312 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamaguchi, T., Eto, M., Harano, K., Kashige, N., Watanabe, K. and Ito, S.: "New Compounds Derived from Dihydropyrazines Having DNA Strand-Breakage Activity"Tetrahedron. 55. 675-686 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiraku, Y., Sugimoto, J., Yamaguchi, T. and Kawanishi, S.: "Oxidative DNA Damage Induced by Aminoacetone, an Amino Acid Metabolite"Archives of Biochemistry and Biophysics. 365. 62-70 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamaguchi, T., Ito, S., Iwase, Y., Watanabe, K. and Harano, K.: "Products from a Novel Reaction of Dihydropyrazines with Vichinaldiamines"Heterocycles. 51. 2305-2309 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tadatoshi Yamaguchi, Shigeru Ito, Yukiko Iwase, Kenji Watanabe, and Kazunobu Harano: "A Diamine-Exchange Reaction of Dihydropyrazines"Heterocycles. 53. 1677-1680 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nobuhiro Kashige, Tadatoshi Yamaguchi, Fumio Miake, and Kenji Watanabe: "Nucleotide Sequence Specificity in DNA Cleavage Caused by Dihydropyrazines, a New Type of DNA Strand-Cleaving Agent,"Biol. Pharm. Bull.. 23. 1281-1286 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tadatoshi Yamaguchi, Shigeru Ito, Nobuko Mibu, and Kunihiro Sumoto: "Reaction of 2,3-butanedione with propylenediamine observed by 1H-NMR spectroscopy"Heterocycles. 57. 11-16 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takatoshi Yamaguchi et al.: "Reaction of 2.3-butanediene with propylenediamine obsereved by iH-NMR spectroscopy"Heterocycles. 57・1. 11-16 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tadatoshi Yamaguchi et. al.: "A Diamine-Exchange Reaction of Dihydropyrazimes"Hetero cycles. 53・8. 1677-1680 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nobuhiro kashige et.al.: "Nucleotide Sequence Speciticity in DNA cleavage Caused by Dihydropyrazimes, a New Type of DNA Strand-cleaving Agent"Biol.Pharm.Bull.. 23・11. 1281-1286 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tadatoshi Yamaguchi et.al.: "Prodlucts trom a Novel Reaction of Dihydropprazime with Vianaldiamine"Heterocycles. 51. 2305-2309 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Yamaguchi et.al.,: "Generation of Free Radicals from Dihydropyrazines with DNA Strand-Breakage Activity" Tetrahedron Letters. 39・45. 8311-8312 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Yamaguchi et.al.,: "New Compounds Derived from Dihydropyrazines Having DNA Strand-Breakage Activity" Tetrahedron. 55. 675-686 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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