2013 Fiscal Year Final Research Report
Sensor mechanism of lipophilic ligands
Project/Area Number |
21248016
|
Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Food science
|
Research Institution | Nagoya University |
Principal Investigator |
UCHIDA Koji 名古屋大学, 生命農学研究科, 教授 (40203533)
|
Project Period (FY) |
2009-04-01 – 2014-03-31
|
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 |
Research Abstract |
Electrophiles in food have been implicated in human health and disease. They react with proteins and generate specific adduct structures that could function as ligands. Isothiocyanates, membrane-permeable electrophiles that form adducts with thiols, have been suggested to have important medical benefits. To gain a chemical insight into the cellular response induced by isothiocyanates, we designed a novel probe, combining an isothiocyanate-reactive group and an alkyne functionality, and revealed that the thiocarbamoylation of proteins occurred in the cells upon exposure to 6-HITC. The target of thiocarbamoylation included heat shock protein 90b (Hsp90b), a chaperone ATPase of the Hsp90 family implicated in protein maturation and targeting. Further study on the thiocarbamoylation of Hsp90b suggested that the formation of 6-HITC-Hsp90b conjugate might cause activation of heat shock factor-1, rapidly signaling a potential heat shock response.
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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: 9943-19957
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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