New synthetic peptide enhances plasminogen activation and thrombolysis

• Project/Area Number: 20590222
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: Kinki University
• Principal Investigator: OKADA Kiyotaka Kinki University, 医学部, 講師 (20185432)
• Co-Investigator(Kenkyū-buntansha): MATSUO Osamu 近畿大学, 医学部, 教授 (40030879) ; KAWAO Naoyuki 近畿大学, 医学部, 助教 (70388510) ; UESHIMA Shigeru 近畿大学, 農学部, 教授 (30193791) ; NAGAI Nobuo 長浜バイオ大学, バイオサイエンス学部, 教授 (90260281)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 血液凝固 / 血液レオロジー / ペプチド / プラスミノーゲン / 線溶系 / プラスミノーゲンアクチベ / 血栓溶解 / マウス / スタヒロキナーゼ

Research Abstract

A new synthetic nonadecapeptide (SP) corresponding to Glu22-Leu40 of staphylokinase molecule bound to plasminogen (Plg) and enhanced the activation of Plg by Plg activator (PA). This binding was completely inhibited by synthetic peptide corresponding to C-terminal region of plasmin B-chain. SP binds to Glu-Plg, and induces structural changes of Glu-Plg. When SP was administrated in mouse thrombosis model, earlier recanalization was observed than in mice with vehicle administration. Thus, SP enhanced Plg activation and induced effective thrombolysis.

Research Products

• [Journal Article] A synthetic peptide derived from staphylokinase enhances plasminogen activator by tissue-type plasminogen activator. (2011)
  • Author(s): Okada K, Ueshima S, Matsuno H, Nagai N, Kawao N, Tanaka M, Matsuo O
  • Journal Title: J Thromb Haemost (Epub ahead of print.)
  • Peer Reviewed
• [Journal Article] Plasminogen/plasmin modulates bone metabolism by regulating the osteoblast and osteoclast function. (2011)
  • Author(s): Kanno Y, Ishisaki A, Kawashita E, Chosa, N, Nakajima K, Nishihara T, Toyoshima K, Okada K, Ueshima S, Matsushita K, Matsuo O, Matsuno H
  • Journal Title: J Biol Chem
  • Peer Reviewed
• [Journal Article] Kawao N, Nagai N, Tamura Y, Okada K, Yano M, Suzuki Y, Umemura K, Ueshima S, Matsuo O (2011)
  • Author(s): Epub ahead of print.
  • Journal Title: Urokinase-type plasminogen activator contributes to heterogeneity of macrophages at the border of damaged site during liver repair in mice. Thromb Haemost(Epub ahead of print.)
  • Peer Reviewed
• [Journal Article] Localization of plasminogen in mouse hippocampus, cerebral cortex, and hypothalamus. (2011)
  • Author(s): Taniguchi Y, Inoue N, Morita S, Nikaido Y, Nakashima T, Nagai N, Okada K, Matsuo O, Miyata S
  • Journal Title: Cell Tissue Res 343 Pages: 303-317
  • Peer Reviewed
• [Journal Article] A synthetic peptide derived from staphylokinase enhances plasminogen activation by tissue-type plasminogen activator. (2011)
  • Author(s): Kiyotaka Okada
  • Journal Title: Journal of Thrombosis and Haemostasis Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Role of plasminogen in macrophage accumulation during liver repair. (2010)
  • Author(s): Kawao N, Nagai N, Okada K, Okumoto K, Ueshima S, Matsuo O
  • Journal Title: Thromb Res 125
  • Peer Reviewed
• [Journal Article] Plasminogen is essential for granulation tissue formation during the recovery process after liver injury in mice. (2010)
  • Author(s): Kawao N, Nagai N, Ishida C, Okada K, Okumoto K, Suzuki Y, Umemura K, Ueshima S, Matsuo O
  • Journal Title: J Thromb Haemost 8 Pages: 1555-1566
  • Peer Reviewed
• [Journal Article] Determination of factor VIII-interactive region within plasmin responsible for plasmin-catalyzed activation and inactivation of factor VIII(a). (2010)
  • Author(s): Nishiya K, Nogami R, Okada K, Matsuo O, Take M, Ogi K, Shima M
  • Journal Title: Thromb Haemost 104 Pages: 105-117
  • Peer Reviewed
• [Journal Article] Role of plasminogen in macrophage accumulation during liver repair (2010)
  • Author(s): Kawao N
  • Journal Title: Thrombolysis Research Web
  • Peer Reviewed
• [Journal Article] Enhancement of fibrinolytic activity in vascular endothelial cells by heterologous expression of adenine nucleotide translocase-1 (2010)
  • Author(s): Ishida C
  • Journal Title: Blood Coagulation and Fibrinolysis Web
  • Peer Reviewed
• [Journal Article] Alpha2-antiplasmin is associated with the progression of fibrosis (2009)
  • Author(s): Kanno Y
  • Journal Title: American Journal of Pathology 176 Pages: 238-245
  • Peer Reviewed
• [Journal Article] Binding of plasminogen to hepatocytes isolated from injured mice liver and nonparenchymal cell-dependent proliferation of hepatocytes. (2008)
  • Author(s): Okada K, Ueshima S, Kawao N, Okamoto C, Matsuo K, Akao M, Seki T, Ariga T, Tanaka M, Matsuo O.
  • Journal Title: Blood Coagul Fibrin 19 Pages: 503-511
  • Peer Reviewed
• [Journal Article] Binding of plasminogen to hepatocytes isolated from injured mouse liver and nonparenchymal-cell-dependent proliferation of hepatocytes. (2008)
  • Author(s): Okada K
  • Journal Title: Blood Coagulation and Fibrinolysis 19 Pages: 503-511
  • Peer Reviewed
• [Journal Article] The absence of uPAR is associated with the progression of dermal fibrosis. (2008)
  • Author(s): Kanno Y
  • Journal Title: Journal of Investigative Dermatology 123 Pages: 2792-2797
  • Peer Reviewed
• [Journal Article] Alpha2-antiplasmin is a critical regulator of angiotensin II-madiated vascular remodeling. (2008)
  • Author(s): Hou Y
  • Journal Title: Arterioscler Thrombosis Vascular Biology 28 Pages: 1257-1262
  • Peer Reviewed
• [Presentation] Syntetic noneecapeptide(SAK22-40)enhances plasminogen activation and thrombolysis. (2010)
  • Author(s): Kiyotaka Okada
  • Organizer: 20th International Congress on Fibrinolysis and Proteolysis
  • Place of Presentation: Amsteraam, The Netherlands
  • Year and Date: 2010-08-27
• [Presentation] Synthetic nonadecapeptide (SAK22-40) enhances plasminogen activation and thrombolysis. (2010)
  • Author(s): Okada K
  • Organizer: 20th Internationl Congress on Fibrinolysis and Proteolysis.
  • Place of Presentation: Amsterdam, The Netherlands.
  • Year and Date: 2010-08-24
• [Presentation] 新規ペプチドの線溶系活性化促進作用の解析 (2010)
  • Author(s): 岡田清孝
  • Organizer: 第33回日本血栓止血学会学術集
  • Place of Presentation: 鹿児島
  • Year and Date: 2010-04-24
• [Presentation] アンギオテンシンII誘発性の血管障害に対するα2-antiplasminの関与 (2009)
  • Author(s): 岡田清孝
  • Organizer: 第32回日本血栓止血学会学術集会
  • Place of Presentation: 小倉
  • Year and Date: 2009-06-05
• [Presentation] 新規ペプチドのプラスミノーゲン活性化促進機序の解析 (2008)
  • Author(s): 岡田清孝
  • Organizer: 第31回日本血栓止血学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2008-11-22
• [Presentation] 新規ペプチドのプラスミノーゲン活性化促進機序の解析 (2008)
  • Author(s): 岡田清孝
  • Organizer: 第31回日本血栓止血学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2008-11-22