Molecular imaging of prion protein by atomic force microscop yand a novel electro-spin-resonance techniques
Project/Area Number |
19380172
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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 |
Applied veterinary science
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Research Institution | Hokkaido University |
Principal Investigator |
I NANAML Osamu Hokkaido University, 大学院・獣医学研究科, 教授 (10193559)
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Co-Investigator(Kenkyū-buntansha) |
INABA Mutsumi 北海道大学, 大学院・獣医学研究科, 教授 (00183179)
HORIUTCHI Motohiro 北海道大学, 大学院・獣医学研究科, 教授 (30219216)
KUWABARA Mikinori 北海道大学, 大学院・獣医学研究科, 名誉教授 (10002081)
ASANUMA Katetoshi 北海道大学, 大学院・獣医学研究科, 准教授 (40332473)
平岡 和佳子 明治大学, 理工学部, 准教授 (00212168)
下山 雄平 室蘭工業大学, 工学部, 教授 (50123948)
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Co-Investigator(Renkei-kenkyūsha) |
HIRAOKA Wakako 明治大学, 理工学部, 教授 (00212168)
SHINOYAMA Yuhei 室蘭工業大学, 工学部, 教授 (50123948)
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Project Period (FY) |
2007 – 2008
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Project Status |
Completed (Fiscal Year 2008)
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Budget Amount *help |
¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000)
Fiscal Year 2008: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2007: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
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Keywords | 人畜共通感染症 / プリオン / 電子スピン共鳴(ESR) / AFM / スピンラベル法 / 動的構造変化 / 部位特異的スピンラベル法 / パルスESR / CJD / 構造生物学 |
Research Abstract |
本研究はブリオン病の原因であるブリオンタンパク質の凝集体変化を新しい方法を用いて明らかにし、今後のプリオン病の病態解明や治療薬の評価方法を開発することを目的とした。このプリオン凝集体への変化を起こすには細胞内低pH器官であるエンドソームで起きることから、pHの低下が必須であると考えられていることからpH7.0の生理条件からpH4.0に変化させたときの構造変化を明らかにした。電子スピン共鳴法、ならびに原子間力顕微鏡を用いて家族性プリオン病でよく見られる変異体プリオンD177NはpH4.0、変性下に置くことで変異を持っていない野生型よりも効率よく線維状の凝集体が起きることが示され。凝集の引き金となる領域がタンパク中心部のβシート付近にあることが明らかとなった。今回の結果はプリオン病の原因タンパク質の構造変化を明らかにしただけでなく、今回用いた新たな方法はプリオン関連病の治療薬の評価系に用いることが可能であると考えられる。
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Report
(3 results)
Research Products
(77 results)
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[Journal Article] Radiation-induced apoptosis of tumor cells is facilitated by inhibition of the interaction between Survivin and Smac / DIABLO2008
Author(s)
Ogura, A., Watanabe, Y., Iizuka, D., Yasui, H., Amitani, M., Kobayashi, S., Kuwabara, M., and Inanami, O.
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Journal Title
Cancer Lett. 259
Pages: 71-81
NAID
Related Report
Peer Reviewed
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[Journal Article] Inhibition of HIF-lalpha by the anticancer drug TAS106 enhances X-ray-induced apoptosis in vitro and in vivo2008
Author(s)
Yasui, H., Ogura, A., Asanuma, T., Matsuda, A., Kashiwakura, I., Kuwabara, M., Inanami, O.
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Journal Title
Br. J. Cancer 299
Pages: 1442-1452
Related Report
Peer Reviewed
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[Journal Article] Visualization of the protective ability of a free radical trapping compound against rat C6 and F98 gliomas with diffusion tensor fiber tractography2008
Author(s)
Asanuma, T., Doblas, S., Tesiram, Y. A., Saunders, D., Cranford, R., Yasui, H., Inanami. O., Smith, N., Floyd, R. A., Kotake, Y. and Towner, R. A.
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Journal Title
J. Magn. Reson. Imaging 28
Pages: 574-587
Related Report
Peer Reviewed
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[Journal Article] Diffusion tensor imaging and fiber tractography of C6 rat glioma2008
Author(s)
Asanuma, T., Doblas, S., Tesiram, Y. A., Saunlers, D., Cranford, R., Pearson, J., Abbott, A., Smith, N. and Towner, R. A.
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Journal Title
J. Magn. Reson. Imaging 28
Pages: 566-573
Related Report
Peer Reviewed
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[Journal Article] The antiproliferative effect of bovine lactoferrin on canine mammary gland tumor cells2008
Author(s)
Yamada, Y., Sato, R., Kobayashi, S., Hankanga, C., Inanami, O., Kuwabara, M., Momota, Y., Tomizawa, N. and Yasuda, J.
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Journal Title
J. Vet. Med. Sci. 70
Pages: 443-448
NAID
Related Report
Peer Reviewed
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[Journal Article] Effect of bovine lactoferrin on functions of activated feline peripheral blood mononuclear cells during chronic feline immunodeficiency virus infection2008
Author(s)
Kobayashi, S., Sato, R., Aoki, T., Omoe, K., Inanami, O., Hankanga, C., Yamada, Y., Tomizawa, N., Yasuda, J. and Sasaki, J.
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Journal Title
J. Vet. Med. Sci. 70
Pages: 429-435
NAID
Related Report
Peer Reviewed
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[Journal Article] X irradiation combined with TNF alpha-related.apoptosis-inducing ligand (TRAIL) reduces hypoxic regions of human gastric adenocarcinoma xenografts in SCID mice2008
Author(s)
Takahashi, M., Yasui, H., Ogura, A., Asanuma, T., Kubota, N., Tsujitani, M., Kuwabara. M. and Inanami, O.
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Journal Title
J. Radiat. Res. 49
Pages: 153-161
Related Report
Peer Reviewed
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[Journal Article] Proinsulin C-peptide abrogates type-1 diabetes-induced increase of renal endothelial nitric oxide synthase in rats2008
Author(s)
Kamikawa, A., Ishii, T., Shimada, K., Makondo, K., Inanami, O., Sakane, Yoshida, T., Saito, M. and Kimura. K.
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Journal Title
Diabetes Metab. Res. Rev. 24
Pages: 331-338
Related Report
Peer Reviewed
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[Journal Article] Individual differences in the radiosensitivity of hematopoietic progenitor cells detected in steady-state human peripheral blood2008
Author(s)
Oriya, A., Takahashi, K., Inanami, O., Miura, T., Abe, Y., Kuwabara. M., Kashiwakura, I.
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Journal Title
J. Radiat. Res. 49
Pages: 113-121
NAID
Related Report
Peer Reviewed
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[Journal Article] A new amphiphilic derivative, N-{[4-(lactobionanaido)methyl]benzylidene} -1,1- dimethy1-2-(octylsulfanyl)ethyIamine N-oxide, has a protective effect against copper-induced fulminant hepatitis in Long-Evans Cinnamon rats at an extremely low concentration compared with its original form alpha-phenyl-N-(tert-butyl) nitrone2007
Author(s)
Asanuma T, Yasui H, Inanami O, Waki K, Takahashi M, Iizuka D, Uemura T, Durand G, Polidori A, Kon Y, Pucci B, Kuwabara M.
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Journal Title
Chem Biodivers 4(9)
Pages: 2253-2267
Related Report
Peer Reviewed
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[Journal Article] A new amphiphilic derivative, N-{[4-(lactobionamido)methyl]benzylidene}-1, 1-dimethyl-2-(octylsulfanyl)ethylamine N-oxide, has a protective effect against copper-induced fulminant hepatitis in Long-Evans Cinnamon rats at an extremely low concentration compared with its original form alpha-phenyl-N-(tert-butyl)nitrone.2007
Author(s)
Asanuma T, Yasui H, Inanami O, Waki K, Takahashi M, Iizuka D, Uemura T, Durand G, Polidori A, Kon Y, Pucci B, Kuwabara M
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Journal Title
Chem Biodivers. 4(9)
Pages: 2253-2267
Related Report
Peer Reviewed
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