Structural analysis of zoonosis-related high-molecular protein aggregation by double electron-electron resonance (DEER) technique

2011 Fiscal Year Final Research Report

• Project/Area Number: 21380185
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied veterinary science
• Research Institution: Hokkaido University
• Principal Investigator: INANAMI Osamu 北海道大学, 大学院・獣医学研究科, 教授 (10193559)
• Co-Investigator(Kenkyū-buntansha): INABA Mustumi 北海道大学, 大学院・獣医学研究科, 教授 (00183179) ; HORIUCHI 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) ; YAMAMORI Tohru 北海道大学, 大学院・獣医学研究科, 准教授 (00512675)
• Project Period (FY): 2009 – 2011
• Keywords: プリオン / 構造生物学 / ESR分光法 / ニトロオキシドプローブ / 距離情報 / 部位特異的スピンラベル法 / 人獣共通感染症

Research Abstract

In this study, to obtain the structural information for this pathological fibrous form of PrPs', we measured the intermolecular distance in the pathological fibrous form with D178N mutation by the site-directed spin labeling (SDSL) with continuous wave (CW) ESR (X-band) and pulsed ESR (Q-band). After the formation of the fibrous structure by exposure to 1M of guanidine hydrochloride in pH4.0, the ESR spectra were measured by CW-ESR. The interspin-distances in pathological fibrous form were measured by continuous wave ESR (CW-ESR) and the four-pulse double electron-electron resonance (DEER) technique. The information of intermolecular distances will be useful to estimate the pathogenic fibrous structure of the familial prion disease, since it is difficult to analyze the macromolecules such as the fibrous protein by NMR or X-ray crystallography.

Research Products

• [Journal Article] A nucleoside anticancer drug, 1-(3-C-ethynyl-Q-D-ribo-pentofuranosyl ) cytosine (TAS106), sensitizes cells to radiation by suppressing BRCA2 expression (2011)
  • Author(s): Meike S., Yamamori T., Yasui H., Eitaki M., Matsuda A., Morimatsu M., Fukushima M., Yamasaki Y., and Inanami O.
  • Journal Title: Molecular Cancer Volume: 10 Pages: 92
  • DOI: doi:10.1186/1476-4598-10-92
  • Peer Reviewed
• [Journal Article] 8-Aminoadenosine enhances radiation-induced cell death in human lung carcinoma A549 cells (2011)
  • Author(s): Meike S., Yamamori T., Yasui H., Eitaki M., Matsuda A., and Inanami O
  • Journal Title: Journal of Radiation Research Volume: 52(4) Pages: 456-463
  • DOI: doi:10.1269/jrr.10188
  • Peer Reviewed
• [Journal Article] Oral administration of bovine lactoferrin upregulates neutrophil functions in a dog with familial 2-integrin-related neutrophil dysfunction. (2011)
  • Author(s): Kobayashi S, Abe Y, Inanami 0, Oda S, Yamauchi K, Hankanga C, Yasuda J, Sato R.
  • Journal Title: Veterinary Immunology and Immunopathology Volume: 143 Pages: 155-161
  • DOI: doi:10.1016/j.vetimm.2011.05.027
  • Peer Reviewed
• [Journal Article] Phosphorylation of p66shc mediates 6-hydroxydopamine cytotoxicity (2011)
  • Author(s): Yamamori, T., Mizobata, A., Saito, Y., Urano, Y., Inanami, O., Irani, K. and Noguchi, N.
  • Journal Title: Free Radical Research Volume: 45 Pages: 342-350
  • DOI: doi:10.3109/10715762. 2010. 532496
  • Peer Reviewed
• [Journal Article] 24(S)-hydroxycholesterol induces neuronal cell death through necroptosis, a form of programmed necrosis. (2011)
  • Author(s): Yamanaka, K., Saito, Y., Yamamori, T., Urano, Y., Noguchi, N.
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 24666-24673
  • DOI: doi:10.1074/jbc.M111.236273
  • Peer Reviewed
• [Journal Article] Regulation of DNA repair enzyme AP endonuclease 1 by lifespan regulation-related protein Sirt1. (2011)
  • Author(s): Yamamori, T. and Irani, K.
  • Journal Title: The Journal of the Hokkaido Veterinary Medical Association Volume: 55 Pages: 45-49
• [Journal Article] Regulation of DNA repair enzyme AP endonuclease 1 by lifespanregulation-related protein Sirt1 (2011)
  • Author(s): Yamamori, T. and Irani, K.
  • Journal Title: The Journal of the Hokkaido Veterinary Medical Association Volume: 55 Pages: 45-49
• [Journal Article] SIRT1 deacetylates APE1 and regulates cellular base excision repair. (2010)
  • Author(s): Yamamori, T., DeRicco, J., Naqvi A, Hoffman TA., Mattagajasingh, I., Kasuno, K., Jung SB, Kim CS., and Irani, K.
  • Journal Title: Nucleic Acids Research Volume: 38 Pages: 832-845
  • Peer Reviewed
• [Journal Article] Super paramagnetic iron oxide MRI shows defective Kupffer cell uptake function in non-alcoholic fatty liver disease. (2010)
  • Author(s): Asanuma, T., Ono, M., kubota, K., Hirose, A., Hayashi, Y., Saibara, T., Inanami, O., Enzan, H., Onishi, S., Kuwabara, M., and Oben, JA.
  • Journal Title: Gut Volume: 59 Pages: 258-266
  • Peer Reviewed
• [Journal Article] Induction of neurite outgrowth by alpha-phenyl-N-tert-butylnitrone through nitric oxide release and Ras-ERK pathway in PC12 cells. (2010)
  • Author(s): Yasui, H., Ito, N., Yamamori, T., Nakamura, H., Okano, J., Asanuma, T., Nakajima, T., Kuwabara, M. , and Inanami, O.
  • Journal Title: Free Radical Research Volume: 44 Pages: 645-654
  • Peer Reviewed
• [Journal Article] A novel copper(II) coordination at His186 in full-length murine prion protein. (2010)
  • Author(s): Watanabe, Y., Hiraoka, W., Igarashi, M., Ito, K., Shimoyama, Y., Horiuchi, M., Yamamori, T., Yasui, H., Kuwabara, M., Inagaki, F., and Inanami, O.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 394 Pages: 522-528
  • Peer Reviewed
• [Journal Article] New insight into hypoxia-targeting cancer therapy. (2010)
  • Author(s): Yasui, H., Yamamori. T., Meike, S., Eitaki, M., Iizuka, D., Kuwabara, M., and Inanami, O.
  • Journal Title: Radiation Biology Research Communications Volume: 45 Pages: 45-57
• [Journal Article] Canine neutrophil dysfunction caused by downregulation of beta2-integrin expression without mutation. (2009)
  • Author(s): Kobayashi S., Sato R., Abe Y., Inanami O., Yasui H., Omoe K., Yasuda J., Hankanga C., Oda S., and Sasaki J.
  • Journal Title: Veterinary Immunology and Immunopathology. Volume: 130 Pages: 187-196
  • Peer Reviewed
• [Journal Article] Redox regulation in radiation-nduced cytochrome c release from mitochondria of human lung carcinoma A549 cells. (2009)
  • Author(s): Ogura A., Oowada S., Kon Y., Hirayama A., Yasui H., Meike S., Kobayashi S., Kuwabara M., and Inanami O.
  • Journal Title: Cancer Letter Volume: 277(1) Pages: 64-71
  • Peer Reviewed
• [Journal Article] Canine neutrophil dysfunction caused by downregulation of beta2-integrin expression without mutation. (2009)
  • Author(s): Kobayashi S, Sato R, Abe Y, Inanami 0, Yasui H, Omoe K, Yasuda J, Hankanga C, Oda S, Sasaki J.
  • Journal Title: Veterinary Immunology and Imunopathology Volume: 130(3-4) Pages: 187-96
  • Peer Reviewed
• [Presentation] Distance measurements of fibrous prion proteins by site-directed spin labeling(SDSL) and ESR spectrouscopy (2012)
  • Author(s): 稲波修
  • Organizer: 20^<th> JSPS Coe-to-core Seminar Internatiional Redox Core Symposium on In Vivo Magnetic Resonance Imaging
  • Place of Presentation: 福岡,西鉄グランドホテル
  • Year and Date: 20120205-0206
• [Presentation] Structual characterization in the mouse prion protein by site-directed spin-labeling and ESR technique (2012)
  • Author(s): 稲波修
  • Organizer: Advanced ESR Studies for New Frontiers in Biofunctional Spin Science and Technology
  • Place of Presentation: 神戸,神戸大瀧川メモリアルホール
  • Year and Date: 2012-11-14
• [Presentation] Novel EPR imaging to visualize cycling hypoxia associated with a defect of vascular integrity integrity in transplanted tumors. (2011)
  • Author(s): 稲波修,安井博宣
  • Organizer: 14th International Congress of Radiation Research
  • Place of Presentation: Warsaw, Memorial to Maria Sklodowska-Curie
  • Year and Date: 2011-08-28
• [Presentation] Idenfication of a novel Cu (II) binding site in full-length murine prionprotein by using ESR/SDSL technique (2010)
  • Author(s): 稲波修
  • Organizer: Asia-Pacific EPR/ESR Symposium
  • Place of Presentation: Jeju
  • Year and Date: 20101010-14
• [Presentation] マウスプリオンタンパク質ヒスチジン186周辺の銅イオン結合部位に関する構造解析 (2009)
  • Author(s): 稲波修
  • Organizer: 第148回日本獣医学会
  • Place of Presentation: 鳥取
  • Year and Date: 20090925-27
• [Remarks]
  • URL: http://www.vetmed.hokudai.ac.jp/organization/radbiol/index.html