Study on the molecular mechanisms of prion secretion from microglial cells

• Project/Area Number: 22580389
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied molecular and cellular biology
• Research Institution: National Institute of Agrobiological Sciences
• Principal Investigator: TAKENOUCHI Takato 独立行政法人農業生物資源研究所, 動物生体防御研究ユニット, 主任研究員 (20292518)
• Co-Investigator(Kenkyū-buntansha): IWAMARU Yoshifumi 独立行政法人農業・食品産業技術総合研究機構・動物衛生研究所, プリオン病研究チーム, 主任研究員 (20355142)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: プリオン / ミクログリア / P2X7 受容体 / P2X7受容体 / P2×7受容体

Research Abstract

Prions are infectious agents composed of protein, and cause transmissible spongiform encephalopathies which are neurodegenerative diseases in mammals. The molecular mechanisms that regulate the spread of prion from cell to cell still remain obscure. In this study, we examined the role of ATP-gated P2X7 receptor (P2X7R) in the release of prions from microglial cells. We found that P2X7R activation promotes the prion release in microglia ingesting prions. We also found that brilliant blue G (BBG) which is known as a P2X7R antagonist reduces prion accumulation both in vitro and in vivo

Research Products

• [Journal Article] Cytochalasin D enhances the accumulation of a protease-resistant form of prion protein in ScN2a Cells: Involvement of PI3 kinase/Akt signaling pathway. (2012)
  • Author(s): Takenouchi T. et al.
  • Journal Title: Cell Biol. Int. Volume: 36 Issue: 12 Pages: 1223-1231
  • DOI: 10.1042/cbi20120329
  • Peer Reviewed
• [Journal Article] Anti-prion activity of Brilliant Blue G. (2012)
  • Author(s): Iwamaru Y*, Takenouchi T*, Murayama Y, Okada H,Imamura M, Shimizu Y, Hashimoto M, Mohri S, Yokoyama T, Kitani H.
  • Journal Title: PLoS ONE Volume: 7 Issue: 5 Pages: 37896-37896
  • DOI: 10.1371/journal.pone.0037896
  • Peer Reviewed
• [Journal Article] The activation of P2X7 receptor induces cathepsin D-dependent production of a 20-kDa form of IL-1b under acidic extracellular pH in LPS-primed microglial cells (2011)
  • Author(s): T akenouchi T, Iwamaru Y, Sugama S, Tsukimoto M, Fujita M, Sekigawa A, Sekiyama K, Sato M, Kojima S, Conti B, Hashimoto M, Kitani H
  • Journal Title: J. Neurochem Volume: 117 Pages: 712-723
  • DOI: 10.1111/j.1471-4159.2011.07240.x
  • Peer Reviewed
• [Journal Article] Cold stress induced morphological microglial activation and increased IL-1β expression in astroglial cells in rat brain (2011)
  • Author(s): Sugama S, Takenouchi T, Fujita M, Kitani H, Hashimoto M
  • Journal Title: J.Neuroimmunol Volume: 233巻 Pages: 29-36
  • Peer Reviewed
• [Journal Article] Reversible conversion of epithelial and mesenchymal phenotypes in SV40 large T antigen-immortalized rat liver cell lines (2010)
  • Author(s): Takenouchi T, Yoshioka M, Yamanaka N, Kitani H.
  • Journal Title: Cell Biol. Int. Rep Volume: 17 Issue: 1 Pages: 1-1
  • DOI: 10.1042/cbr20100001
  • Peer Reviewed
• [Journal Article] Reversible conversion of epithelial and mesenchymal phenotypes in SV40 large Tantigen-immortalized rat liver cell lines (2010)
  • Author(s): Takenouchi T, Yoshioka M, Yamanaka N, Kitani H
  • Journal Title: Cell Biol.Int.Rep Volume: 17巻
  • Peer Reviewed
• [Presentation] プリオン感染N2a細胞での異常プリオン蛋白蓄積におけるアクチン骨格及びPI3キナーゼ経路の関与 (2013)
  • Author(s): 竹之内敬人,岩丸祥史,今村守一,佐藤充,横山隆,毛利資郎,木谷裕
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 仙台
  • Year and Date: 2013-03-26
• [Presentation] P2X7 receptor-mediated pathways (2012)
  • Author(s): Takenouchi T, Iwamaru Y, Tsukimoto M, Sato M, Kojima S, Hashimoto M, Kitani H.
  • Organizer: involved in the production and release of a 20-kDa form of IL-1β from LPS-primed microglial cells. Purine 2012
  • Place of Presentation: 福岡
  • Year and Date: 2012-05-31
• [Presentation] P2X7 receptor-mediated pathways involved in the production and release of a 20-kDa form of IL-1β from LPS-primed microglial cells. (2012)
  • Author(s): Takenouchi T, Iwamaru Y, Tsukimoto M, Sato M, Kojima S, Hashimoto M, Kitani H
  • Organizer: Purine 2012
  • Place of Presentation: 福岡
• [Presentation] P2X7受容体活性化に伴うミクログリアからの20-kDa IL-1βフラグメントの産生機構 (2011)
  • Author(s): 竹之内敬人、岩丸祥史、洲鎌秀永、月本光俊、佐藤充、小島周二、橋本款、木谷裕
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] Anti-prion activityof Brilliant blue G (2011)
  • Author(s): Iwamaru Y, Takenouchi T, Imamura M, Shimizu Y, Murayama Y, Mohri S, Yokoyama T, Kitani H.
  • Organizer: an antagonist of the ATP-sensitive receptor P2X7. Asian Pacific Prion Symposium 2011
  • Place of Presentation: 軽井沢
  • Year and Date: 2011-07-11
• [Presentation] Brilliant blue G (2011)
  • Author(s): Iwamaru Y, Takenouchi T, Imamura M, Shimizu Y, Murayama Y, Mohri S, Yokoyama T, Kitani H.
  • Organizer: an antagonist of the ATP sensitive receptor P2X7 prevents prion accumulation. Prion 2011
  • Place of Presentation: モントリオール、カナダ
  • Year and Date: 2011-05-17
• [Presentation] Brilliant blue G, an antagonist of the ATP sensitive receptor P2X7 prevents prion accumulation (2011)
  • Author(s): Iwamaru Y, Takenouchi T, Imamura M, Shimizu Y, Murayama Y, Mohri S, Yokoyama T, Kitani H
  • Organizer: Prion 2011
  • Place of Presentation: モントリオール、カナダ
• [Presentation] Anti-prion activity of Brilliant blue G, an antagonist of the ATP-sensitive receptor P2X7 (2011)
  • Author(s): Iwamaru Y, Takenouchi T, Imamura M, Shimizu Y, Murayama Y, Mohri S, Yokoyama T, Kitani H
  • Organizer: Asian Pacific Prion Symposium 2011
  • Place of Presentation: 軽井沢
• [Presentation] P2X7受容体活性化に伴うミクロクリアからの20-kDa IL-1βフラグメントの産生機構 (2011)
  • Author(s): 竹之内敬人、岩丸祥史、洲鎌秀永、月本光俊、佐藤充、小島周二、橋本款、木谷裕
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] P2X7受容体阻害剤Brilliant Blue Gは持続感染細胞におけるプリオン増殖を阻害する (2010)
  • Author(s): 岩丸祥史,竹之内敬人,清水善久,今村守一,村山裕一,横山隆,木谷裕
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] P2X7受容体阻害剤Brilliant Blue Gは持続感染細胞におけるプリオン増殖を阻害する (2010)
  • Author(s): 岩丸祥史, 竹之内敬人, 清水善久, 今村守一, 村山裕一, 横山隆, 木谷裕
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: ホートアイランド(神戸)
  • Year and Date: 2010-12-08
• [Book] Role of autophagy in P2X7 receptor-mediated maturation and unconventional secretion of IL-1β in microglia. AUTOPHAGY: Cancer, Other Pathologies, Inflammation, Immunity, and Infection (2013)
  • Author(s): Takenouchi T, Sekiyama K, Tsukimoto M, Iwamaru Y, Fujita M, Sugama S, Kitani H, Hashimoto M.
  • Publisher: Elsevier (in press)
• [Book] AUTOPHAGY: Cancer, Other Pathologies, Inflammation, Immunity, and Infection (CHAPTER: ROLE OF AUTOPHAGY IN P2X7 RECEPTOR-MEDIATED MATURATION AND UNCONVENTIONAL SECRETION OF IL-1β IN MICROGLIA) (2013)
  • Author(s): Takenouchi T, Sekiyama K, Tsukimoto M, Iwamaru Y, Fujita M, Sugama S, Kitani H, Hashimoto M
  • Publisher: Elsevier