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Prion protein binds to aldolase A in intracellular vesicles of bovine intestinal M cells

Research Project

Project/Area Number 24380150
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Applied animal science
Research InstitutionTohoku University

Principal Investigator

ASO Hisashi  東北大学, (連合)農学研究科(研究院), 教授 (50241625)

Co-Investigator(Kenkyū-buntansha) WATANABE Koichi  東北大学, 大学院農学研究科, 助教 (80261494)
KITAZAWA Haruki  東北大学, 大学院農学研究科, 准教授 (10204885)
OKADA Natsumi  東北大学, 技術一般職員 (10621584)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2012: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Keywordsプリオン / アルドラーゼA / M細胞 / 腸管免疫 / マウス腸管上皮細胞 / ウシ腸管上皮細胞 / 侵入機構 / 抗体阻害 / 牛腸管上皮細胞株 / マウス腸管上皮細胞株 / 侵入 / トランスサイトーシス / プロテオーム解析 / 輸送小胞 / 組織解析 / aldolase A
Outline of Final Research Achievements

The exact mechanism by which BSE crosses the intestinal barrier is not clear. M cells are able to incorporate large numbers of PrP coated magnetic particles into intracellular vesicles, which we collected. The results of 2-DE show a specific protein associated with the PrP-coated particles. This protein was identified as aldolase A, a glycolytic pathway enzyme, using LC-MS/MS analysis. Aldolase A was synthesized and secreted by BIE cells, and increased during M cell differentiation. In the villi of the bovine intestine, aldolase A was detected on the surface of the epithelium and in the mucus droplet of goblet cells. In the FAE of bovine jejunal and ileal Peyer’s patches, aldolase A was localized on the surface and the apical part of the M cells. The binding of rbPrP to aldolase A was clearly detected and inhibited by pre-treatment of anti-aldolase A antibody. Therefore, aldolase A-positive M cells may play a key role in the invasion of BSE into the body.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (36 results)

All 2015 2014 2013 2012 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (17 results) (of which Invited: 1 results) Book (1 results) Remarks (2 results)

  • [Journal Article] The toll-like receptor family protein RP105/MD-1 complex is involved in the immunoregulatory effect of exopolysaccharides from Lactobacillus plantarum N14.2015

    • Author(s)
      Murofushi, Y., J. Villena, P. Kanmani, H. Kitazawa et al.
    • Journal Title

      Mol. Immunol.

      Volume: 64 Issue: 1 Pages: 63-75

    • DOI

      10.1016/j.molimm.2014.10.027

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Advanced Application of Porcine Intramuscular Adipocytes for Evaluating Anti-Adipogenic and Anti-Inflammatory Activities of Immunobiotics.2015

    • Author(s)
      Masahiko Suzuki, Asuka Tada, Paulraj Kanmani, Hitoshi Watanabe, Hisashi Aso, Yoshihito Suda, Tomonori Nochi, Kenji Miyazawa, Kazutoyo Yoda, Fang He, Masataka Hosoda, Tadao Saito, Julio Villena, Haruki Kitazawa
    • Journal Title

      PLoS ONE

      Volume: 10 (3) Issue: 3 Pages: 1-20

    • DOI

      10.1371/journal.pone.0119644

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transportation of sublingual antigens across sublingual ductal epithelial cells to the ductal antigen-presenting cells in mice.2015

    • Author(s)
      Nagai Y, Shiraishi D, Tanaka Y, Nagasawa Y, Ohwada S, Shimauchi H, Aso H, Endo Y, Sugawara S.
    • Journal Title

      Clinical and Experimental Allergy

      Volume: 45 Issue: 3 Pages: 677-686

    • DOI

      10.1111/cea.12329

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lactobacillus delbrueckii TUA4408L and its extracellular polysaccharides attenuate Enterotoxigenic Escherichia coli induced inflammatory response in porcine intestinal epitheliocytes via Toll-like receptor-2 and 4.2014

    • Author(s)
      Wachi, S., P. Kanmani, H. Kitazawa et al.
    • Journal Title

      Mol. Nutr. Food Res.

      Volume: 58 Issue: 10 Pages: 2080-2093

    • DOI

      10.1002/mnfr.201400218

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Immunobiotic Lactobacillus rhamnosus strains differentially modulate antiviral immune response in porcine intestinal epithelial and antigen presenting cells.2014

    • Author(s)
      Villena, J., H. Aso, H. Kitazawa et al.
    • Journal Title

      BMC Microbiol.

      Volume: 14(126) Issue: 1 Pages: 1-14

    • DOI

      10.1186/1471-2180-14-126

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Myostatin alters glucose transporter-4 (GLUT4) expression in bovine skeletal muscles and myoblasts isolated from double muscled (DM) and normal muscled (NM) Japanese shorthorn cattle.2014

    • Author(s)
      H. Takahashi, K. Sato, T. Yamaguchi, M. Miyake, H. Watanabe, Y. Nagasawa, E. Kitagawa, S. Terada, M. Urakawa, M. T. Rose, C. D. McMahon, K. Watanabe, S. Ohwada, T. Gotoh, H. Aso
    • Journal Title

      Domestic Animal Endocrinology

      Volume: 48 Pages: 62-68

    • DOI

      10.1016/j.domaniend.2014.01.007

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of peripheral 5-HT on glucose and lipid metabolism in wether sheep.2014

    • Author(s)
      Watanabe H., Kitazawa H., Watanabe K., Aso H. 他
    • Journal Title

      PLoS ONE

      Volume: 9 Issue: 2 Pages: 1-12

    • DOI

      10.1371/journal.pone.0088058

    • NAID

      120005435471

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunoregulatory Effect of Bifidobacteria Strains in Porcine Intestinal Epithelial Cells through Modulation of Ubiquitin-Editing Enzyme A20 Expression.2013

    • Author(s)
      Tomosada, Y., H. Kitazawa, et al.
    • Journal Title

      PLoS ONE

      Volume: 8(3) Issue: 3 Pages: 1-12

    • DOI

      10.1371/journal.pone.0059259

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Advanced application of bovine intestinal epithelial cell line for evaluating regulatory effect of lactobacilli against heat-killed enterotoxigenic Escherichia coli-mediated inflammation.2013

    • Author(s)
      Takanashi, N. et al.
    • Journal Title

      BMC Microbiol.

      Volume: 13(54) Issue: 1 Pages: 1-16

    • DOI

      10.1186/1471-2180-13-54

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Advanced application of porcine intestinal epithelial cells for the selection of immunobiotics modulating toll-like receptor 3-mediated inflammation2012

    • Author(s)
      Villena, J., H.Kitazawa, et al
    • Journal Title

      J.Microbiol.Immunol.Infect.

      Volume: (未定)(印刷中) Issue: 6 Pages: 474-481

    • DOI

      10.1016/j.jmii.2012.04.005

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of myostatin in neural cells of the olfactory system.2012

    • Author(s)
      Syunsuke Iwasaki
    • Journal Title

      Molecular Neurobiology

      Volume: 47 Issue: 1 Pages: 1-8

    • DOI

      10.1007/s12035-012-8342-1

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AMPK activation by AICAR inhibits myogenic differentiation and myostatin expression in cattle.2012

    • Author(s)
      Masato Miyake
    • Journal Title

      Cell and Tissue Research

      Volume: 349 Issue: 2 Pages: 615-623

    • DOI

      10.1007/s00441-012-1422-8

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunobiotic Lactobacillus jensenii Modulates the Toll-Like Receptor 4-Induced Inflammatory Response via Negative Regulation in Porcine Antigen-Presenting Cells2012

    • Author(s)
      Villena, J., H.Kitazawa, et al
    • Journal Title

      Clin.Vac.Immunol.

      Volume: (未定)(印刷中) Issue: 7 Pages: 1038-1053

    • DOI

      10.1128/cvi.00199-12

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A newly established bovine intestinal epithelial cell line is effective for in vitro screening of potential antiviral immunobiotic microorganisms for cattle.2012

    • Author(s)
      Chiba E., 他
    • Journal Title

      Research in Veterinary Science

      Volume: 93 Issue: 2 Pages: 688-694

    • DOI

      10.1016/j.rvsc.2011.10.002

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of a Lactobacilli, Oligosaccharide and Organic Germanium Intake on the Immune Responses of Mice2012

    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 76 Issue: 2 Pages: 375-377

    • DOI

      10.1271/bbb.110655

    • NAID

      10030400214

    • ISSN
      0916-8451, 1347-6947
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunobiotic Lactobacillus jensenii elicit anti-inflammatory activity in porcine intestinal epithelial cells by modulating negative regulators of the toll-like receptor signaling pathway2012

    • Author(s)
      Shimazu, T., H.Aso, Y.Suda, Y.Kawai, T.Saito, H.Kitazawa, et al
    • Journal Title

      Infect.Immun.

      Volume: 80 Issue: 1 Pages: 276-288

    • DOI

      10.1128/iai.05729-11

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 新規イムノバイオティック評価指標の網羅的探索2015

    • Author(s)
      小林永和・石塚好将・麻生久・齋藤忠夫・北澤春樹
    • Organizer
      第119回日本畜産学会大会
    • Place of Presentation
      宇都宮市、宇都宮大学
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] ブタ腸管由来樹状細胞におけるイムノバイオティクスの取り込み解析2015

    • Author(s)
      月田耕一郎・飯田ひかる・大和田修一・遠野雅徳・須田義人・麻生久・牧野聖也・池上秀二・齋藤忠夫・北澤春樹
    • Organizer
      第119回日本畜産学会大会
    • Place of Presentation
      宇都宮市、宇都宮大学
    • Year and Date
      2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] ウシ腸管M細胞における解糖系酵素アルドラーゼAの合成と分泌2014

    • Author(s)
      長澤裕哉・盛田彰太郎・日高湧介・鈴木 京・渡邉一史・渡邊康一・大和田修一・野地智法・北澤春樹・今村守一・横山 隆・堀内基広・坂口末廣・麻生 久
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      札幌市、北海道大学
    • Year and Date
      2014-09-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新生仔ブタ腸管に認められる初乳取り込み能を持つ上皮細胞の組織学的研究2014

    • Author(s)
      田彰太郎・長澤裕哉・渡邊康一・野地智法・麻生 久
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      札幌市、北海道大学
    • Year and Date
      2014-09-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 炎症性腸疾患における腸上皮細胞由来シクロフィリンAの作用解明2013

    • Author(s)
      染谷俊輔、, 他
    • Organizer
      第116回日本畜産学会
    • Place of Presentation
      名古屋、安田女子大学
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腸管M細胞における解糖系酵素アルドラーゼAを介したプリオン蛋白質取り込み機構2013

    • Author(s)
      長澤裕哉、, 他
    • Organizer
      第116回日本畜産学会
    • Place of Presentation
      名古屋、安田女子大学
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] ブタ末梢血由来樹状細胞の分化誘導とイムノバイオティック評価系への利用性2013

    • Author(s)
      高橋卓也、, 他
    • Organizer
      第116回日本畜産学会
    • Place of Presentation
      名古屋、安田女子大学
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] Role of aldolase A in transcytosis of intestinal M cells.2012

    • Author(s)
      Nagasawa Y., 他
    • Organizer
      American Society for Cell Biology Annual Meeting.
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2012-12-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] 腸管M細胞における解糖系酵素アルドラーゼAを介した抗原取り込み機構2012

    • Author(s)
      長澤裕哉、, 他
    • Organizer
      第154回日本獣医学会学術集会
    • Place of Presentation
      岩手大学
    • Year and Date
      2012-09-14
    • Related Report
      2012 Annual Research Report
  • [Presentation] マウスDSS誘導大腸炎と白血球遊走因子シクロフィリンAとの関連性2012

    • Author(s)
      染谷俊輔、, 他
    • Organizer
      第154回日本獣医学会学術集会
    • Place of Presentation
      岩手大学
    • Year and Date
      2012-09-14
    • Related Report
      2012 Annual Research Report
  • [Presentation] 高抗病性ランドレース豚の免疫担当臓器におけるサイトカイン発現の特性解析2012

    • Author(s)
      菅原静夏、, 他
    • Organizer
      第62回東北畜産学会大会
    • Place of Presentation
      秋田県立大学
    • Year and Date
      2012-08-29
    • Related Report
      2012 Annual Research Report
  • [Presentation] Prion protein binding proteins of bovine intestine M cell.2012

    • Author(s)
      Nagasawa Y., 他
    • Organizer
      Asian Pacific Prion Symposium 2012
    • Place of Presentation
      横浜
    • Year and Date
      2012-06-30
    • Related Report
      2012 Annual Research Report
  • [Presentation] ウシパイエル板M細胞における解凍系酵素アルドラーゼAを介した異常型プリオン蛋白質取り込み機構

    • Author(s)
      長澤裕哉、他
    • Organizer
      第118回日本畜産学会大会
    • Place of Presentation
      つくば市、国際会館
    • Related Report
      2013 Annual Research Report
  • [Presentation] 解糖系酵素アルドラーゼAを介する腸管M細胞の異常型プリオン蛋白質侵入機構

    • Author(s)
      麻生 久
    • Organizer
      第6回共同利用・共同研究「酵素学研究拠点」シンポジウム
    • Place of Presentation
      徳島市、徳島大学疾患酵素学研究センター
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] マウス腸管M細胞における解糖系酵素アルドラーゼAを介した異常型プリオン蛋白質取り込み機構

    • Author(s)
      長澤裕哉、他
    • Organizer
      第156回日本獣医学会学術集会
    • Place of Presentation
      岐阜市、岐阜大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] The role of aldolase A in transcytosis of PrPSc by intestinal M cells.

    • Author(s)
      Nagasawa Y.,他
    • Organizer
      Asian Pacific Prion Symposium 2013
    • Place of Presentation
      Sasebo, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Cyclophilin A is a specific marker of M cells in bovine intestinal Peyer's patches.

    • Author(s)
      Nagasawa Y.,他
    • Organizer
      NIH-Tohoku University-JSPS Symposium
    • Place of Presentation
      仙台市、艮陵会館
    • Related Report
      2013 Annual Research Report
  • [Book] The Expression of Cytokeratins in Bovine Intestinal Microfold (M) Cells. In : Cytokeratins-Tools in Oncology, Gerhard Hamilton (Ed.)2012

    • Author(s)
      Kanaya T., 他
    • Publisher
      InTech, ISBN: 978-953-51-0047-8
    • Related Report
      2012 Annual Research Report
  • [Remarks] 東北大学大学院農学研究科機能形態学分野

    • URL

      http://www.agri.tohoku.ac.jp/keitai/index-j.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 動物機能科学講座・機能形態学分野

    • URL

      http://www.agri.tohoku.ac.jp/keitai/index-j.html

    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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