2013 Fiscal Year Final Research Report
Chemical Biology of Reactive Oxygen Species Ligand Receptor Regulation
| Project Area | Signaling functions of reactive oxygen species |
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| Project/Area Number |
20117007
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Nagoya University |
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Principal Investigator |
UCHIDA Koji 名古屋大学, 生命農学研究科, 教授 (40203533)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBATA Takahiro 名古屋大学, 生命農学研究科, 助教 (80447838)
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| Project Period (FY) |
2008-11-13 – 2013-03-31
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| Keywords | 脂溶性リガンド / プロテオミクス / センサー分子 / 分子プローブ / 受容体 |
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| Research Abstract |
We established some new protein adductions of proteins by lipid-derived electrophilic aldehydes. To verify the presence of the protein-bound ligands in vivo, we raised a monoclonal antibody against the ligands, characterized the epitopes, and immunohistochemically demonstrated the presence of the ligands in vivo. In addition, we developed high performance liquid chromatography with on-line electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS)-based quantification methods and showed evidence that the ligands are indeed accumulated in vivo. We also established the danger signal function of these ligands. Furthermore, we characterized the multi-specificity mechanism of innate antibodies that recognize the modified proteins as antigenic ligands and established that they contribute to the removal of apoptotic cells and biological defense.
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[Journal Article] An apoptosis-associated mammary protein deficiency leads to enhanced production of IgM antibodies against multiple damage-associated molecules2013
Author(s)
Chikazawa, M., Otaki, N., Shibata, T., Yasueda, T., Matsuda, T., and Uchida, K.
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Journal Title
PLoS ONE
Volume: 8
Pages: e68468
DOI
Peer Reviewed
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[Journal Article] Multi-specificity of IgM antibodies raised against advanced glycation end products: Involvement of electronegative potential of antigens2013
Author(s)
Chikazawa, M., Otaki, N., Shibata, T., Miyashita, H., Kawai, Y., Maruyama, S., Toyokuni, S., Kitaura, Y., Tsukasa Matsuda, and Uchida, K.
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Journal Title
J. Biol. Chem
Volume: 288
Pages: 13204-13214
DOI
Peer Reviewed
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[Journal Article] Identification of 4-hydroxy-2-nonenal-histidine adducts that serve as ligands for human lectin-like oxidized LDL receptor-12012
Author(s)
Kumano-Kuramochi, M., Shimozu, Y., Wakita, C., Ohnishi-Kameyama, M., Shibata, T., Matsunaga, S., Takano-Ishikawa, Y., Watanabe, J., Goto, M., Xie, Q., Komba, S., Uchida, K., and Machida, S.
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Journal Title
Biochem. J
Volume: 442
Pages: 171-180
DOI
Peer Reviewed
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[Journal Article] Lipid peroxidation modification of protein generates Ne-(4-oxononanoyl)lysine as a pro-inflammatory ligand2011
Author(s)
Shibata, T., Shimozu, Y., Wakita, C., Shibata, N., Kobayashi, M., Machida, S., Kato, R., Itabe, H., Zhu,X., Sayre, L. M., and Uchida, K.
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Journal Title
J. Biol. Chem
Volume: 286
Pages: 19943-19957
DOI
Peer Reviewed
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[Journal Article] 4-Hydroperoxy-2-nonenal is not just an intermediate, but a reactive molecule that covalently modifies proteins to generate unique intramolecular oxidation products2011
Author(s)
Shimozu, Y., Hirano, K., Shibata, T., Shibata, N., and Uchida, K.
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Journal Title
J. Biol. Chem
Volume: 286
Pages: 29313-29324
DOI
Peer Reviewed
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[Journal Article] Transthiocarbamoylation of proteins by thiolated isothiocyanates2011
Author(s)
Shibata, T., Kimura, Y., Mukai, A., Mori, H., Ito, S., Asaka, Y., Oe, S., Tanaka, H., Takahashi, T., and Uchida, K.
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Journal Title
J. Biol. Chem
Volume: 286
Pages: 42150-42161
DOI
Peer Reviewed
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[Journal Article] D^<12>-Prostaglandin J_2 as a product and ligand of human serum albumin: Formation of an unusual covalent adduct at His1462010
Author(s)
Yamaguchi, S., Aldini, G., Ito, S., Morishita, N., Shibata, T., Vistoli, G., Carini, M., and Uchida, K.
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Journal Title
J. Am. Chem. Soc
Volume: 132
Pages: 824-832
DOI
Peer Reviewed
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[Journal Article] Lipid peroxidation generates a body odor component trans-2-nonenal covalently bound to protein in vivo2010
Author(s)
Ishino, K., Wakita, C., Shibata, T., Toyokuni, S., Machida, S., Matsuda, S., Matsuda, T., and Uchida, K.
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Journal Title
J. Biol. Chem
Volume: 285
Pages: 15302-15313
DOI
Peer Reviewed
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[Journal Article] Identification of a lipid peroxidation product as the source of oxidation-specific epitopes recognized by anti-DNA autoantibodies2010
Author(s)
Otaki, N., Chikazawa, M., Nagae, R., Shimozu, Y., Shibata, T., Ito, S., Takasaki, Y., Fujii, J., and Uchida, K.
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Journal Title
J. Biol. Chem
Volume: 285
Pages: 33834-33842
DOI
Peer Reviewed
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[Journal Article] Stereochemical configuration of 4-hydroxy-2-nonenal-cysteine adducts and their stereoselective formation in a redox-regulated protein2009
Author(s)
Wakita, C., Maeshima, T., Yamazaki, A., Shibata, T., Ito, S., Akagawa, M., Ojika, M., Yodoi, J., and Uchida, K.
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Journal Title
J. Biol. Chem
Volume: 284
Pages: 28810-28822
DOI
Peer Reviewed
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