Proteasomal dysfunction and pathology
Project/Area Number |
22590353
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | Hokkaido University |
Principal Investigator |
TOMARU Utano 北海道大学, 大学院・医学研究科, 准教授 (20360901)
|
Co-Investigator(Kenkyū-buntansha) |
ISHIZU Akihiro 北海道大学, 大学院・保健科学研究院, 教授 (60321957)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | プロテアソーム / 老化 / 免疫 / 胸腺プロテアソーム / モデル動物 / 老化関連疾患 / T細胞 / 胸腺 / COPD / 免疫異常 / 脂肪代謝 |
Research Abstract |
In this study, we established a transgenic (β5t-Tg) mouse model with decreased proteasomal chymotrypsin-like activity. β5t-Tg mice exhibited a shortened lifespan and age-related phenotypes. When β5t-Tg mice were fed a high-fat diet, they developed more pronounced obesity and hepatic steatosis than wild-type mice. It has been known that proteasome plays an important role in the immune system, and β5t-Tg mice show abnormal T cell maturation. Our results demonstrate that decreased proteasomal chymotrypsin-like activity affects longevity and aggravates age-related metabolic disorders such as obesity and hepatic steatosis, and may correlate to the pathogenesis of immune-related disorders
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Report
(4 results)
Research Products
(82 results)
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[Journal Article] Mechanism of Fc γreceptor-mediated trogocytosis-based false-positive results in flow cytometry2012
Author(s)
Masuda, S., Iwasaki, S., Tomaru, U., Sato, J., Kawakami, A., Ichijo, K., Sogo, S., Baba, T.,Katsumata, K., Kasahara, M. and Ishizu, A
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Journal Title
PLoS ONE
Volume: 7(12)
Issue: 12
Pages: e52918-e52918
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Decrease of peripheral and intestinal NKG2A-positive T cells in patients with ulcerative colitis2012
Author(s)
Katsurada, T., Kobayashi, W., Tomaru, U.,Baba, T., Furukawa, S., Ishizu, A., Takeda, K., Sakamoto, N., Asaka, M., Takeda, H. and Kasahara, M
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Journal Title
PLoS ONE7
Volume: (9)
Issue: 9
Pages: e44113-e44113
DOI
Related Report
Peer Reviewed
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[Journal Article] Abnormal conformation and impaired degradation of NETs induced by propylthiouracil: Implication of disordered NETs in MPO-ANCA-associated vasculitis2012
Author(s)
Nakazawa, D., Tomaru, U., Suzuki, A., Hasegawa, R., Kobayashi, T., Nishio, S., Kasahara, M. and Ishizu, A
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Journal Title
Arthritis Rheum
Volume: 64(11)
Issue: 11
Pages: 3779-3787
DOI
Related Report
Peer Reviewed
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[Journal Article] Proteasome subunit β5t expression in cervical ectopic thymoma2012
Author(s)
Tomaru, U., Yamada, Y., Ishizu, A., Kuroda, T., Matsuno, Y. and Kasahara, M
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Journal Title
J. Clin. Pathol.
Volume: 65(9)
Issue: 9
Pages: 858-859
DOI
Related Report
Peer Reviewed
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[Journal Article] Decreased proteasomal activity causes age-related phenotypes and promotes the development of metabolic abnormalities2012
Author(s)
Tomaru U, Takahashi S, Ishizu A, Miyatake Y, Gohda A, Suzuki S, Ono A, Ohara J, Baba T, Murata S, Tanaka K, Kasahara M
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Journal Title
Am.J.Pathol.
Volume: 180
Issue: 3
Pages: 963-972
DOI
Related Report
Peer Reviewed
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[Journal Article] Comparative genomic analysis of theproteasome β5t subunit gene: implications for the origin and evolution of thymoproteasomes2011
Author(s)
Sutoh, Y., Kondo, M., Ohta, Y., Ota, T., Tomaru, U., Flajnik, MF., Kasahara, M
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Journal Title
Immunogenetics
Volume: 64
Pages: 49-58
Related Report
Peer Reviewed
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[Journal Article] Expression of proteasome subunit β5t in thymic epithelial tumors2011
Author(s)
Yamada, Y., Tomaru, U., Ishizu, A., Kiuchi, T., Marukawa, K., Matsuno, Y., Kasahara, M
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Journal Title
Am J Surg Pathol
Volume: 35
Pages: 1296-1304
NAID
Related Report
Peer Reviewed
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[Journal Article] High prevalence of multiple human papillomavirus infection in Japanese patients with invasive uterinecervical cancer2011
Author(s)
Watari, H., Michimata, R., Yasuda, M., Ishizu, A., Tomaru, U., Xiong, Y., Hassan, MK., Sakuragi, N
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Journal Title
Pathobiology
Volume: 78
Pages: 220-226
Related Report
Peer Reviewed
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[Journal Article] A. Plasma-dependent, antibody- and Fcγ receptor-mediated translocation of CD8 molecules from T cells to monocytes2010
Author(s)
Iwasaki, S., Masuda, S., Baba, T., Tomaru, U., Katsumata, K., Kasahara, M. and Ishizu
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Journal Title
Cytometry A
Volume: 79
Pages: 45-56
NAID
Related Report
Peer Reviewed
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[Journal Article] Frequency and pattern of expression of the stem cell marker CD133 have strong prognostic effect on the surgical outcome of colorectal cancerpatients2010
Author(s)
Takahashi, S., Kamiyama, T., Tomaru, U., Ishizu, A., Shida, T., Osaka, M., Sato, Y., Saji, Y., Ozaki, M., Todo, S
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Journal Title
Oncol. Rep
Volume: 24
Pages: 1201-1212
Related Report
Peer Reviewed
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[Journal Article] Invasive group A streptococcal infection in pregnancy2010
Author(s)
Yamada, T., Yamada, T., Yamamura, MK., Katabami, K., Hayakawa, M., Tomaru, U., Shimada, S., Morikawa, M., Seki, T., Ariga, S., Ishikawa, K., Ikebe, T., Gando, S., Minakami, H
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Journal Title
J. Infect
Volume: 60
Pages: 417-424
Related Report
Peer Reviewed
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[Journal Article] Cyclic AMP response element-binding protein is implicated in IL-6 production from arthritic synovial cells2010
Author(s)
Ishizu, A., Abe, A., Miyatake, Y., Baba, T., Iinuma, C., Tomaru, U., Yoshiki, T
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Journal Title
Mod. Rheumatol
Volume: 20
Pages: 134-138
NAID
Related Report
Peer Reviewed
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[Presentation] Abnormal conformation and impaired degradation of neutrophil extracellular traps (NETs) induced by propylthiouracil (PTU): Implication of disordered NETs inMPO-ANCA-associated vasculitis(MPO-AAV)2012
Author(s)
Nakazawa, D., Tomaru, U., Nishio, S., Atsumi, T., Kasahara, M. and Ishizu, A
Organizer
第41回日本免疫学会学術集会
Place of Presentation
神戸国際展示場(兵庫県)
Year and Date
2012-12-07
Related Report
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[Presentation] Skewed T cell development in mice with aberrant expression of thymoproteasome2012
Author(s)
Ohara, J., Tomaru, U., Ishizu, A., Konno, S., Suzuki, S., Murata, S., Tanaka, K. and Kasahara, M
Organizer
第41回日本免疫学会学術集会
Place of Presentation
神戸国際会議場(兵庫県)
Year and Date
2012-12-05
Related Report
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[Presentation] プロテアソームの機能異常による病理作用2010
Author(s)
高橋里美,外丸詩野,小野綾子,合田文,鈴木小百合,宮武由甲子,小原次郎,村田茂穂,田中啓二,石津明洋,笠原正典
Organizer
第43回北海道病理談話会
Place of Presentation
北海道大学(札幌市)
Year and Date
2010-10-23
Related Report
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[Presentation] Serum-dependent, antibody and Fcγ receptor-mediated translocation of CD8 molecules from T cells to monocytes2010
Author(s)
Iwasaki, S., Masuda, S., Baba, T., Katsumata, K., Tomaru, U., Kasahara, M. and Ishizu, A
Organizer
14th International Congress of Immunology
Place of Presentation
神戸ホ゜ートヒ゜アホテル(兵庫県)
Related Report
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[Presentation] Skewed T cell development in mice with ectopic expression of thymoproteasome2010
Author(s)
Tomaru, U., Suzuki, S., Ishizu, A., Takahashi, S., Ohara, J., Miyatake, Y., Murata, S., Tanaka, K. and Kasahara, M.
Organizer
14th International Congress of Immunology
Place of Presentation
神戸ホ゜ートヒ゜アホテル(兵庫県)
Related Report
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[Presentation] プロテアソームの機能異常による病理作用2010
Author(s)
高橋里美,外丸詩野,鈴木小百合,小野綾子,宮武由甲子,風巻拓,小原次郎,村田茂穂,田中啓二,石津明洋,笠原正典
Organizer
第99回日本病理学会総会
Place of Presentation
京王フ゜ラサ゛ホテル(東京都)
Related Report
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[Presentation] 胸腺プロテアソームの異所性発現によるT細胞分化の異常2010
Author(s)
鈴木小百合,外丸詩野,高橋里美,小原次郎,風巻拓,小野綾子,宮武由甲子,村田茂穂,田中啓二,石津明洋,笠原正典
Organizer
第99回日本病理学会総会
Place of Presentation
京王フ゜ラサ゛ホテル(東京都)
Related Report
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