Development of gram-positive bacteria sepsis therapy by inhibition of bacterial proteases.
Project/Area Number |
18390125
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
|
Research Institution | Kumamoto University |
Principal Investigator |
IMAMURA Takahisa Kumamoto University, 大学院・医学薬学研究部, 准教授 (20176499)
|
Co-Investigator(Kenkyū-buntansha) |
梅山 秀明 北里大学, 薬学部, 教授 (20050619)
|
Project Period (FY) |
2006 – 2008
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Project Status |
Completed (Fiscal Year 2008)
|
Budget Amount *help |
¥10,760,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000)
|
Keywords | 黄色ブドウ球菌 / プロテアーゼ / 阻害剤 / 血管漏出 / 敗血性ショック / システインプロテアーゼ / 敗血症 / 治療 / ショック / 凝固 / 線溶 / 欠損株 |
Research Abstract |
黄色ブドウ球菌放出病原プロテアーゼstaphopain A とBの立体構造に基づいて活性中心部の鍵穴に当てはまる化学物質を30万種類程度の試薬リストからコンピュータを使ってドッキング計算より選出し、阻害効果を調べた。Staphopain BについてはKi値が数10μM程度の阻害物質しか得られなかったが、Aに対して最も強い阻害効果をもつchemical #11は、Ki値1.3μMで拮抗型阻害を示し、本菌敗血性ショック発症に直結するstaphopain Aの血管漏出作用を20 μM でほぼ完全に抑制した。さらに他の細菌や細胞、血漿由来のプロテアーゼに対してもその種類や基質特異性とは無関係に阻害効果がみられたことから、プロテアーゼが関係する疾患への治療を含めた多方面への応用性が示唆された。
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Report
(4 results)
Research Products
(70 results)
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[Journal Article] Lysine-specific gingipain promotes lipopolysaccharides- and active vitamin D_3-induced osteoclast differentiation by degrading osteoprotegerin2009
Author(s)
Yasuhara, R., Miyamoto, Y., Takami, M., Imamura, T., Potempa, J., Yoshimura, K., & Kamijo, R.
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Journal Title
Biochem. J 419
Pages: 159-166
Related Report
Peer Reviewed
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[Journal Article] Thrombin in synovial fluid as a marker of synovial inflammation: a definite measurement by ELISA and correlation with VEGF2008
Author(s)
Kitamoto, Y., Nakamura, E., Kudo, S., Tokunaga, H., Murakami, E., Noguchi, K., & Imamura, T.
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Journal Title
Clinica Chimica Acta 389
Pages: 159-160
Related Report
Peer Reviewed
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[Journal Article] Prostate expression of endothelins and their receptors in rat growth. Reprod2008
Author(s)
Wada. Y., Takahashi, W., Latifpour, J., Weiss, R. M., Matsumoto, K., Matsui, K., Yamada, G., and *Imamura, T.
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Journal Title
Fertil. Develop 20
Pages: 750-759
Related Report
Peer Reviewed
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[Journal Article] Production of C5a by ASP, a serine protease released from Aeromonas sobria2008
Author(s)
Nitta, H., Imamura, T., Wada, Y., Irie, A., Kobayashi, H., Okamoto, K., & Baba, H
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Journal Title
J. Immunol 181
Pages: 3602-3608
Related Report
Peer Reviewed
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[Journal Article] Impaired plasma clotting induction through fibrinogen degradation by ASP, a serine protease released from Aeromonas sobria2008
Author(s)
Imamura, T., Nitta, H., Wada, Y., Kobayashi, H., & Okamoto, K
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Journal Title
FEMS Mirobiol. Lett 284
Pages: 35-42
Related Report
Peer Reviewed
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[Journal Article] Coexistence of serus cystadenoma and ductal adenocarcinoma in the pancreas : A case report and literature review2008
Author(s)
Nitta, H., Hirota, M., Ohkado, A., Motomura, Y., Chikamoto, A., Shibata, M., Takamori, H., Kanemitsu, K., Imamura, T., Yamamoto, T., & Baba, H
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Journal Title
Pancreas 36
Pages: 218-219
Related Report
Peer Reviewed
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[Journal Article] Modified technique for improving tubeless cutaneous ureterostomy using the Ariyoshi method2008
Author(s)
Wada, Y., Kikuchi, K., Suenaga, T., Imamura, T., Matsumoto, K., & Kodama, K
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Journal Title
Int. J. Urol 15
Pages: 144-150
Related Report
Peer Reviewed
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[Journal Article] Activation of prothrombin by ASP, a serine protease released from Aeromonas sobria2007
Author(s)
Nitta, H., Kobayashi, H., Irie, A., Baba, H., Okamoto, K., & Imamura, T
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Journal Title
FEBS lett 581
Pages: 5935-5939
Related Report
Peer Reviewed
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[Journal Article] Arginine-specific gingipains from Porphyromonas gingivalis deprive protective functions of secretory leukocyte inhibitor in periodontal tissue2006
Author(s)
Into, T., Inomata, M., Kanno, Y., Matsuyama, T., Machigashira, M., Izumi,Y., Imamura, T., Nakashima, M., Noguchi, T., & Matsushita, K
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Journal Title
Clin. Exp.Immunol 145
Pages: 545-554
Related Report
Peer Reviewed
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[Journal Article] DX-9065a inhibits proinflammatory events induced by gingipains and factor Xa2006
Author(s)
Matsushita, K., Imamura, T., Tomikawa, M., Tancharoen, S., Tatsuyama, S., & Maruyama, I
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Journal Title
J. Periodont. Res 41
Pages: 148-156
Related Report
Peer Reviewed
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[Journal Article] Selcetive inhibition of Porphyromonas gingivalis growth by a factor Xa inhibitor, DX-9065a2006
Author(s)
17.Matsushita, K., Imamura, T., Tancharoen, S., Tatsuyama, S., Tomikawa, M.,Travis, J., Potempa, J., Torii, M., & Maruyama, I
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Journal Title
J. Periodont. Res 41
Pages: 171-176
Related Report
Peer Reviewed
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