2001 Fiscal Year Final Research Report Summary
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
| Project/Area Number |
12490017
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
広領域
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
FUJII Noriko Research Reactor Institute, Kyoto University, Associate Professor, 原子炉実験所, 助教授 (90199290)
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| 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)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Aging / UV irradiation / Gamma-ray irradiation / D-amino acid / Racemization / Isomerization / Lens / Post-translational Modification |
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| 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
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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
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[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
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[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)
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「研究成果報告書概要(和文)」より
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[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
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[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
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