Effect of Clostridium perfringens beta-toxin on receptor-signal transduction pathway of immune cells

• Project/Area Number: 19590462
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Tokushima Bunri University
• Principal Investigator: NAGAHAMA Masahiro Tokushima Bunri University, 薬学部, 准教授 (40164462)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Keiko 徳島文理大学, 薬学部, 助教 (90170315)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ウエルシュ菌 / β毒素 / THP-1細胞 / ホスホリパーゼC / 脂質ラフト / ポアー形成 / ラフト / 細胞毒性

Research Abstract

ウエルシュ菌β毒素の免疫系細胞のシグナル伝達系に対する作用を検討すると、毒素は細胞膜の脂質ラフトに結合しオリゴマーを形成後、内因性ホスホリパーゼC(PLC)を活性化し、産生されたイノシトール3リン酸が細胞内Ca^<2+>濃度を上昇させることが判明した。その後、Ca^<2+>を介する一連のシグナル伝達系が働き、TNF-α遊離が促進する。すなわち、β毒素は、内因性PLCを活性化後、サイトカインの遊離や細胞毒性を誘導すると考えられる。

Research Products

• [Journal Article] Effect of erythromycin on biological activities induced by Clostridium perfringens alpha-toxin (2008)
  • Author(s): Masataka Oda, Masahiro Nagahama, Jun Sakurai. (著者11人、8番目)
  • Journal Title: J. Pharmacol. Exp. Ther. 327 Pages: 934-940
  • Peer Reviewed
• [Journal Article] Structural basis of actin recognition and arginine ADP-ribosylation by Clostridium perfringens iota-toxin (2008)
  • Author(s): Hideaki Tsuge, Masahiro Nagahama, Jun Sakurai. (著者9人、2番目)
  • Journal Title: Proc. Natl. Acad. Sci. USA, 105 Pages: 7399-7404
  • Peer Reviewed
• [Journal Article] Involvement of tumour necrosis factor-. in Clostridium perfringens .-toxin-induced plasma extravasation in mice (2008)
  • Author(s): Masahiro Nagahama, Aatsushi Kihara, Jun Sakurai. (著者5人、1番目)
  • Journal Title: Br. J. Pharmacol. 153 Pages: 1296-1302
  • Peer Reviewed
• [Journal Article] The relationship between the metabolism of sphingomyelin species and hemolysis of sheep erythrocytes induced by Clostridium perfringens alpha-toxin (2008)
  • Author(s): Masataka Oda, Masahiro Nagahama, Jun Sakurai. (著者10人、8番目)
  • Journal Title: J. Lipid Res. 49 Pages: 1039-1047
  • Peer Reviewed
• [Journal Article] Role of Ca2+-binding motif in cytotoxicity induced by Clostridium perfringens iota-toxin (2008)
  • Author(s): Keiko Kobayashi, Masahiro Nagahama, Jun Sakurai. (著者8人、1と2番目)
  • Journal Title: Microb. Pathogen. 44 Pages: 265-270
  • Peer Reviewed
• [Journal Article] Effect of erythromycin on biological activities induced by Clostridium perfrinsens alpha-toxin. (2008)
  • Author(s): Masataka Oda
  • Journal Title: J. Pharmacol. Exp. Ther. 327 Pages: 934-940
  • Peer Reviewed
• [Journal Article] Structural basis of actin recognition and arginine ADP-ribosylation by Clostridium perfringens iota-toxin. (2008)
  • Author(s): Hideaki Tsuge
  • Journal Title: Proc. Nat. Acad. Sci. U.S.A. 105 Pages: 7399-7404
  • Peer Reviewed
• [Journal Article] The relationship between the metabolism of sphingomyelin species andhemolysis of sheep erythrocytes induced by Clostridium perfringens alpha-toxin. (2008)
  • Author(s): Masataka Oda
  • Journal Title: J. Lipid Res. 49 Pages: 1039-1047
  • Peer Reviewed
• [Journal Article] Structural basis of actin recognition and arginine ADP-ribosylation by Clostridium perfingens iota-toxin (2008)
  • Author(s): Hideaki Tsuge
  • Journal Title: Proc.Nat.Acad.Sci.U.S.A (in press)
  • Peer Reviewed
• [Journal Article] The relationship between the metabolism of sphingomyelin species and hemolysis of sheep erythrocytes induced by Clostridiium perfringens alpha-toxin (2008)
  • Author(s): Masataka Oda
  • Journal Title: J.Lipid Res 49 Pages: 1039-1047
  • Peer Reviewed
• [Journal Article] Involvement of tumor necrosis factor-alpha in Clostridium perfringens beta-toxin-induced plasma extravasation in mice (2008)
  • Author(s): Masahiro Nagahama
  • Journal Title: Br.J.Pharmacol 153 Pages: 1296-1302
  • Peer Reviewed
• [Journal Article] Effect of unsaturated bonds in the sn-2 acyl chain of phosphatidylcholine on the membrane- damaging action of Clostridium perfringens alpha-toxin toward liposomes (2007)
  • Author(s): Masahiro Nagahama, Akiko Otsuka, Jun Sakurai. (著者8人、1番目)
  • Journal Title: Biochim. Biophys. Acta 1768 Pages: 2940-2945
  • Peer Reviewed
• [Journal Article] Enteritis necroticans 'pigbel' in a Japanese diabetic adult (2007)
  • Author(s): Tomomichi Matsuda, Masahiro Nagahama Shinya Tanaka. (著者9人、8番目)
  • Journal Title: Pathol. Int. 57 Pages: 622-626
  • Peer Reviewed
• [Presentation] ウエルシュ菌ε毒素のMDCK細胞に対するATP涸渇と細胞毒性の解析 (2009)
  • Author(s): 永浜政博
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-26
• [Presentation] ウエルシュ菌ε毒素のMDCK細胞に対するATP涸渇と細胞毒性の解析 (2009)
  • Author(s): 永浜政博
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都・京都国際会館
  • Year and Date: 2009-03-26
• [Presentation] ウエルシュ菌TpeL毒素でグルコシル化される低分子量Gタンパク質の検討 (2009)
  • Author(s): 永浜政博
  • Organizer: 第82日本細菌学会総会
  • Place of Presentation: 名古屋
• [Presentation] ボツリヌス菌C2毒素の細胞内輸送経路の解析 (2008)
  • Author(s): 永浜政博
  • Organizer: BMB200
  • Place of Presentation: 神戸
• [Presentation] ウエルシュ菌TpeL毒素の細胞毒性機構の解析 (2008)
  • Author(s): 大窪晶子、永浜政博
  • Organizer: 第20回微生物シンポジウム
  • Place of Presentation: 岐阜
• [Presentation] ウエルシュ菌β毒素のマウス皮膚血管透過性作用とTNF-αの関係 (2008)
  • Author(s): 永浜政博
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
• [Presentation] ウエルシュ菌イオタ毒素のイオタa成分とアクチンの結晶解析 (2008)
  • Author(s): 小林敬子、永浜政博
  • Organizer: 第81日本細菌学会総会
  • Place of Presentation: 京都
• [Presentation] ウエルシュ菌イオタ毒素のイオタa成分とアクチンの結合解析 (2007)
  • Author(s): 岩本 忍、永浜政博
  • Organizer: 第54回毒素シンポジウム
  • Place of Presentation: 大阪府泉佐野
• [Book] 化学療法の領域25巻5号 6.細菌由来スフィンゴミエリナーゼの構造と機能、p74-80 (2009)
  • Author(s): 櫻井純、小田真隆、永浜政博
  • Publisher: 医薬ジャーナル社
• [Book] 化学療法の領域25巻5号特集 : 細菌毒素タンパクの新たな理解へ向けて3. 細菌由来スフインゴミエリナーゼの構造と機能 (2009)
  • Author(s): 櫻井純
  • Total Pages: 7
  • Publisher: 医薬ジャーナル社