Analysis of gastric mucosal defense mechanisms involving gastrointestinal tract-specific calpains

• Project/Area Number: 20780106
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Food science
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: HATA Shoji Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 主任研究員 (10392375)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: カルパイン / 胃粘膜損傷 / カルシウム / 胃粘膜防御 / カルパイン複合体 / タンパク質分解 / 胃粘膜

Research Abstract

Calpains are Ca^<2+->dependent cytosolic proteases that are indispensable for various cellular processes. Here we show that mice with mutations in the genes for two gastrointestinal tract-specific calpains 8 and 9 are susceptible to stress-induced gastric injury. Moreover, these calpains form a stable complex, in which both molecules are essential for activity. Gastric mucosal integrity depends on a complex defense system that acts in the face of a variety of irritants, including alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs), and Helicobacter pylori. The continuous or improper ingestion of these irritants often leads to serious gastropathies. Our results might therefore contribute to the development of new therapeutic strategies for human gastropathies induced by irritants.

Research Products

• [Journal Article] Dynamic distribution of muscle-specific calpain adapts to physical stress and its defects cause muscular dystrophy. (2010)
  • Author(s): Ojima K, Kawabata Y, Nakao H, Nakao K, Doi N, Kitamura F, Ono Y, Hata S, Suzuki H, Kawahara H, Witt C, Ottenheijm C, Labeit S, Granzier H, Toyama-Sorimachi N, Sorimachi M, Suzuki K, Maeda T, Abe K, Aiba A, Sorimachi H
  • Journal Title: J. Clin. Invest (in press)
  • Peer Reviewed
• [Journal Article] Skeletal muscle-specific calpain is an intracellular Na+-dependent protease. (2010)
  • Author(s): Ono Y, Ojima K, Torii F, Takaya E, Doi N, Nakagawa K, Hata S, Abe K, Sorimachi H
  • Journal Title: J. Biol. Chem (in press)
  • Peer Reviewed
• [Journal Article] Expanding members and roles of calpain superfamily and their genetically modified animals. (2010)
  • Author(s): Sorimachi H, Hata S, Ono Y
  • Journal Title: Exp. Anim (in press)
  • NAID: 130000419250
  • Peer Reviewed
• [Journal Article] Calpain (2010)
  • Author(s): Sorimachi H., Hata S., Ono Y.
  • Journal Title: Encyclopedia of Biological Chemistry (2nd Edition) (印刷中)
• [Journal Article] Muscle RING-Finger protein MuRF1 as a connector of muscle energy metabolism and protein synthesis. (2008)
  • Author(s): Koyama S, Hata S(equally contributed first author), Witt C, Ono Y, Lerche S, Ojima K, Chiba T, Doi N, Kitamura F, Tanaka K, Abe K, Witt S, Rybin V, Gasch A, Franz T, Labeit S, Sorimachi H
  • Journal Title: J. Mol. Biol 376 Pages: 1224-1236
  • Peer Reviewed
• [Journal Article] Muscle RING-Finger protein MuRFl as a connector of muscle energy metabolism and rotein synthesis. (2008)
  • Author(s): Koyama S, Hata S., et al.
  • Journal Title: Journal of Molecular Biology 376 Pages: 1224-1236
  • Peer Reviewed
• [Journal Article] Calpain 8/nCL-2 and Calpain 9/nCL-4 constitute an active protease complex, G-calpain, involved in gastric mucosal defense.
  • Author(s): Hata S, Abe M, Suzuki H, Kitamura F, Toyama-Sorimachi N, Abe K, Sakimura K, Sorimachi H
  • Journal Title: PLoS Genet 2010(in press)
  • Peer Reviewed
• [Presentation] 二種類の胃腸特異的カルパインの複合体形成と胃粘膜防御への関与 (2009)
  • Author(s): 秦勝志、北村ふじ子, 他
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2009-10-23
• [Presentation] 二種類の胃腸特異的カルパインの複合体形成と胃粘膜防御への関与 (2009)
  • Author(s): 秦勝志
  • Organizer: 日本生化学会関東支部会
  • Place of Presentation: 筑波
  • Year and Date: 2009-06-20
• [Presentation] 二種類の胃腸特異的カルパインの複合体形成と胃粘膜防御への関与 (2009)
  • Author(s): 秦勝志
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸
• [Presentation] 胃特異的カルパインnCL-2/calpain 8の酵素学的解析 (2008)
  • Author(s): 秦勝志
  • Organizer: 日本蛋白質科学会
  • Place of Presentation: 東京
• [Book] Calpain.(eds., M.D. Lane and W.J. Lennarz, Encyclopedia of Biological Chemistry 2nd Edition) (2010)
  • Author(s): Sorimachi H., Hata S, Ono Y
  • Publisher: Elsevier(in press)
• [Book] カルパイン(木幡裕一、城石俊彦、芹川忠夫、田中啓二、米川博通 編, モデル動物利用マニュアル) (2010)
  • Author(s): 反町洋之、秦勝志、小野弥子
  • Publisher: (株)LIC(印刷中)
• [Book] モデル動物利用マニュアル(木幡裕一、城石俊彦、芹川忠夫、田中啓二、米川博通編) (2010)
  • Author(s): 反町洋之、秦勝志、小野弥子
  • Publisher: (株)LIC(印刷中)