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老化・紫外線・放射線によるタンパク質中のD-β-アスパラギン酸生成とその機構

Research Project

Project/Area Number 12490017
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 広領域
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

FUJII Noriko  Research Reactor Institute, Kyoto University, Associate Professor, 原子炉実験所, 助教授 (90199290)

Co-Investigator(Kenkyū-buntansha) SHIMO-OKA Tadashi  Life Science Center, Asahi Techno Glass Corp, Director, ライフサイエンスセンター, センター長(研究職)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥12,300,000 (Direct Cost: ¥12,300,000)
KeywordsAging / UV irradiation / Gamma-ray irradiation / D-amino acid / Racemization / Isomerization / Lens / Post-translational Modification
Research Abstract

I) INVERSION AND ISOMERIZATION OF ASP-151 AND ASP-58 RESIDUE IN HUMAN ALPHA A-CRYSTALLIN FROM NORMALAGED LENSES. Although proteins are generally composed entirely of L-amino acids, we showed that Asp-151 and Asp-58 in alpha A-crystallin from aged human lens is inverted to the biologically uncommon D-beta-isomer to a high degree during aging. The drastic changes started at birth, with about 45 % of normal L- alpha -Asp lost by the 30 year range. These modifications of the Asp residue likely affects the three-dimensional packing array of the lens proteins.
II) CORRELATION BETWEEN LOSS OF CHAPERONE-LIKE ACTIVITY, AND OXIDATION, ISOMERIZATION AND RACEMIZATION OF GAMMA-IRRADIATED ALPHA-CRYSTALLIN. Alpha-crystallin possesses a molecular chaperone-like activity that prevents proteins from aggregating ; however, the mechanism of this activity is not well known. Here we have gamma-irradiated alpha-crystallin and studied the relationship between the decrease in chaperone-like activity and modific … More ations such as oxidation, isomerization and racemization of amino acids in this molecule. We found that the chaperone-like activity of alpha-crystallin decreased with increasing gamma irradiation. The secondary structure of the irradiated alpha-crystallin did not change, however its tertiary structure of the alpha-crystallin seems to change more than 1000Gy irradiation. Depending on the radiation dose, Met- 1 of alpha A-crystallin was oxidized to methionine sulfoxide. In addition, Asp-151 of alpha A-crystallin was isomerized to the beta-Asp form after irradiation, and racemization of Asp-151 was decreased. Thus, loss of the fe chaperone-like activity of alpha-crystallin is related to changes in its isomerization, oxidation and racemization.
III) BIOLOGICALLY UNCOMMON D-BETA-ASPARTIC ACID-CONTAINING PROTEIN IN ELASTIC FIBERS OF SUN DAMAGED SKIN. We have prepared the antibody agaist D-beta-Asp containing protein and examined its immunoreactivity in skin. The antibody recognized disintegrated elastic fibers in sun-exposed skin. Western plot analysis of the proteins isolated from sun-damaged skin demonstrated that the polypeptide with 50kDa was immunoreactive with the antibodies for D-beta-Asp containing protein and elastin. This result suggests that UV irradiation significant racemization and isomerization of Asp resideus in proteins of elastic fibers and the unusual proteins were accumulated during aging. We propose that the antibody could be a useful indicator for sun damage of the skin. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Fujii, N.: "D-amino acids in livin2 higher organisms"Origin of Life and Evolution of the Biosphere. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii, N., Matumoto S., Hiroki, K., Takemoto, L.J.: "Inversion and isomerization of Asp-58 residue in human alpha A-crystallin from normal aged lenses and cataractous lenses"Biochim.Biohys.Acta. 1549. 179-187 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii, N., Hiroki, K., Matsumoto, S., Masuda, K., Inoue, M., Tanaka, Y., Awakura, M., Akaboshi, M.: "Correlation Between Loss of Chaperone-like Activity, and Oxidation, Isomerization and Racemization of Gamma-ray Irradiated Alpha-crystallin"Photochem. Photobiol.. 74. 477-482 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kodama, M, Ogiso, M., Fujii, N., Tateishi, T., Wana B., Ojima, S., Matsuura, T., Hara, Y., Saishin, M., Yamauchi, A.: "3 D Structure of the Vitreous Body"Viva Origino. 29. 45-54 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takemoto, L.J., Fujii, N., Boyle, D.: "Mechanism of Asparagine Deamidation During Human Senile Cataractogenesis"Exp. Eye Res.. 72. 559-563 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii, N., Takemoto, L.J., (et al.4): "The comparison of the D-aspartic acid contents in alphaA-crystallin from normal and age-matched cataractous human lenses"Biochem. Biophys. Res. Comm.. 278. 408-413 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mizuno, A.Fujii, N., (et al.3): "Changes of secondary structure detected by laser Raman spectroscopy in model peptides of human alpha A-crysrallin by a substitution of D-aspartyl residues for L-aspartyl residues in the peptides"Jpn J. Ophthalmol. 44. 354-359 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii, N., Shimo-oka, T., (et al.4): "Localization of Biologically Uncommon D-β-Aspartate Containing αA-Crystallin in Human Eye Lens"Molecular Vision. 6. 1-5 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimada, A., Fujii, N., Nakamura I.: "Increasingly activity change of tryptophanase irradiated with a low dose of gammarays"Viva Origino. 28. 65-76 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii, N., Momose Y., (et al.2): ""Modification of αA-crystallin obtained from aged and X-ray irradiated mouse lenses. in "The Role of Radiation and Origin of Life""Kyoto Univ. Academic Press, Kyoto. 18 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii, N.: "D-amino acids in living higher organisms"Origin of Life and Evolution of the Biosphere. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] <Fujii. N.>__________-, Matumoto S., Hiroki, K. and Takemoto, L. J.: "Inversion and isomerization of Asp-58 residue in human alpha A-crystallin from normal aged lenses and cataractous lenses"Biochim. Biophys. Acta.. 1549. 179-187 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] <Fujii, N.>__________-, Hiroki, K., Matsumoto, S., Masuda, K., Inoue, M., Tanaka, Y., Awakura, M. and Akaboshi, M: "Correlation Between Loss of Chaperone-like Activity, and Oxidation, Isomerization and Racemization of Gamma-ray Irradiated Alpha-crystallin"Photochem. Photobiol.. 74. 477-482 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kodama, M, Ogiso, M., <Fuiii.N.>__________-, Tateishi. T., Wang, B., Ojima, S.,Matsuura, T., Hara, Y., Saishin, M. and Yamauchi, A: "3D Structure of the Vitreous Body"Viva Origina. 29. 45-54 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takemoto,L. J., <Fujii. N.>___________-, and Boyle, D.: "Mechanism of Asparagine Deamidation During Human Senile Cataractogenesis"Exp. EyeRes.. 72. 559-563 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] <Fujii. N.>__________-, Takemoto,L. J, (et al.4).: "The comparison of the D-aspartic acid contents in alphaA-crystallin from normal and age-matched cataractous human lenses"Biochem. Biophys. Res. Comm.. 278. 408-413 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mizuno, A. <Fujii. N.>__________-, (et al.3): "Changes of secondary structure detected bylaser Roman spectroscopy in model peptides of human alpha A-ctystallin by a substitution ofD-aspartyl residues for L- aspartyl residues in the peptides."Jpn J. Ophthalmol. 44. 354-359 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] <Fujii. N.>__________-, Shimo-oka, T., (et al.4): "Localization of Biologically Uncommon D-β-Aspartate Containing αA-Crystallin in Human Eye Lens"Molecular Vision. 6. 1-5 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shimada, A., <Fujii. N.>__________- and Nakatnura I.: "Increasingly activity change of tryptophanase irradiated with a low dose of gamma-rays"Viva Origino. 28. 65-76 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] <Fujii. N.>__________-, Momose Y., (et al.2): "Modification ofαA-crystallin obtained from aged and X-ray irradiated mouse lenses, in "The Role of Radiation and Origin of Life""Kyoto Univ. Academic Press, Kyoto. 18 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii, N.: "D-amino acids in living higher organisms"Origin of Life and Evolution of the Biosphere. in press. (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujii, N., Matumoto S., et al.2).: "Inversion and isomerization of Asp-58 residue in human alpha A-crystallin from normal aged lenses and cataructous lenses"Biochem. Biophys. Acta. 1549. 179-187 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujii, N., Hiroki, K., (et al.6).: "Carrelation Between Loss of Chaperone-like Activity, and Oxidation, Isomerization and Racemization of Gamma-ray Irradiated Alpha-crystallin"Photochem. Photobiol.. 74. 477-482 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kodama, M, Ogiso, M., Fujii, N., (et al.7): "3 D Structure of the Vitreous Body"Viva Origino. 29. 45-54 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takemoto, L.J., Fujii, N., Boyle, D.: "Mechanism of Asparagine Deamidation During Human Senile Cataractogenesis"Exp. Eye Res.. 72. 559-563 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujii,N.: "A view on to the L-amino acid world through the "D-amino acid-scope""Advanves in Biophysics. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takemoto,L.J.,Fujii,N.,and Boyle,D.: "Mechanism of asparagine deamidation during human senile cataractogenesis."Exp.Eye Res.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujii,N.,Takemoto,L.J., (et al.4).: "The comparison of the D-aspartic acid contents in alphaA-crystallin from normal and age-matched cataractous human lenses."Biochem.Biophys.Res.Comm.. 278. 408-413 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mizuno,A.Fujii,N., (et al.3): "Changes of secondary structure detected by laser Raman spectroscopy in model peptides of human alpha A-crystallin by a substitution of D-aspartyl residues for L-aspartyl residues in the peptides."Jpn J.Ophthalmol. 44. 354-359 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujii,N.,Shimo-oka,T., (et al.4): "Localization of Biologically Uncommon D-β-Aspartate Containing αA-Crystallin in Human Eye Lens."Molecular Vision. 6. 1-5 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimada,A.,Fujii,N.and Nakamura I.: "Increasingly activity change of tryptophanase irradiated with a low dose of gamma-rays."Viva Origino. 28. 65-76 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujii,N.,Momose Y., (et al.2): ""Modification of αA-crystallin obtained from aged X-ray irradiated mouse lenses.in "The Role of Radition and Origin of Life""Kyoto Univ.Academic Press, Kyoto. 18 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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