Molecular mechanism of platelet hyper-aggregation in patients with type 2 diabetes and development of method for the diagnosis

• Project/Area Number: 20590565
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Gifu University
• Principal Investigator: TOKUDA Haruhiko Gifu University, 医学系研究科, 非常勤講師 (10397325)
• Co-Investigator(Kenkyū-buntansha): KOZAWA Osamu 岐阜大学, 医学系研究科, 教授 (90225417)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 糖尿病 / 血小板 / 血栓 / ストレス蛋白質 / ストレス

Research Abstract

We developed a novel diagnostic method of platelet hyper-aggregation in patients with type 2 diabetes mellitus (DM). Our results strongly suggest that the phosphorylation levels of collagen-induced p38 mitogen-activated protein kinase (MAPK) and p44/p42 MAPK represent the hyperaggregability of platelets, and the quantification of phospho-p38 MAPK would be a new and useful diagnostic biomarker of platelet hyper-aggregation in DM patients.

Research Products

• [Journal Article] Antithrombin III reduces collagen-stimulated granule secretion of PDGF-AB and the release of soluble CD40 ligand from human platelets. (2010)
  • Author(s): Doi T, Adachi S, Matsushima-Nishiwaki R, Kato H, Enomoto Y, Natsume H, Kato K, Mizutani J, Otsuka T, Tokuda H, Akamatsu S, Iwama T, Kozawa O, Ogura S.
  • Journal Title: Int.J.Mol.Med. 26 Pages: 387-392
  • NAID: 120006341935
  • Peer Reviewed
• [Journal Article] Mechanism of collagen-induced release of 5-HT, PDGF-AB and sCD4OL from human platelets : role of HSP27 phosphorylation via p44/p42 MAPK. (2010)
  • Author(s): Kato H, Adachi S, Doi T, Matsushima-Nishiwaki R, Minamitani C, Akamatsu S, Enomoto Y, Tokuda H, Otsuka T, Iwama T, Kozawa O, Ogura S.
  • Journal Title: Thromb.Res. 126 Pages: 39-43
  • Peer Reviewed
• [Journal Article] Thromboxane A_2 promotes soluble CD40 ligand release from human platelets. (2010)
  • Author(s): Enomoto Y, Adachi S, Matsushima-Nishiwaki R, Doi T, Niwa M, Akamatsu S, Tokuda H, Ogura S, Yoshimura S, Iwama T, Kozawa O.
  • Journal Title: Atherosclerosis 209 Pages: 415-421
  • Peer Reviewed
• [Journal Article] Raloxifene enhances spontaneous microaggregation of platelets through up-regulation of p44/p42 MAP kinase : a case report. (2010)
  • Author(s): Tokuda H, Harada A, Adachi S, Matsushima-Nishiwaki R, Natsume H, Minamitani C, Mizutani J, Otsuka T, Kozawa O.
  • Journal Title: Osteoporosis Int. 21 Pages: 189-193
  • Peer Reviewed
• [Journal Article] Mechanism of collagen-induced release of 5-HT, PDGF-AB and sCD4OL from human platelets : role of HSP27 phosphorylation via p44/p42 MAPK. (2010)
  • Author(s): Kato H, Tokuda H, et al.
  • Journal Title: Thromb. Res. Volume: 126 Pages: 39-43
  • Peer Reviewed
• [Journal Article] Thromboxane A2 promotes soluble CD40 ligand release fromhuman platelets. (2010)
  • Author(s): Enomoto Y, Tokuda H, et al.
  • Journal Title: Atherosclerosis Volume: 209 Pages: 415-421
  • Peer Reviewed
• [Journal Article] Antithrombin III reduces collagen-stimulated granule secretion of PDGF-AB and the release of soluble CD40 ligand from human platelets. (2010)
  • Author(s): Doi T, Tokuda H, et al.
  • Journal Title: Int. J. Mol. Med. Volume: 26 Pages: 387-392
  • NAID: 120006341935
  • Peer Reviewed
• [Journal Article] Antithrombin III suppresses ADP-induced platelet granule secretion : inhibition of HSP27 phosphorylation. (2009)
  • Author(s): Doi T, Adachi S, Takai S, Matsushima-Nishiwaki R, Kato H, Enomoto Y, Minamitani C, Otsuka T, Tokuda H, Akamatsu S, Iwama T, Kozawa O, Ogura S.
  • Journal Title: Arch.Biochem.Biophys. 489 Pages: 62-67
  • Peer Reviewed
• [Journal Article] αB-crystallin extracellularly suppresses ADP-induced granule secretion from human platelets. (2009)
  • Author(s): Enomoto Y, Adachi S, Matsushima-Nishiwaki R, Niwa M, Tokuda H, Akamatsu S, Doi T, Kato H, Yoshimura S, Ogura S, Iwama T, Kozawa O.
  • Journal Title: FEBS Lett. 583 Pages: 2464-2468
  • Peer Reviewed
• [Journal Article] Level of collagen-induced p38 MAP kinase activation is a biomarker of platelet hyper-aggregation in patients with diabetes mellitus. (2009)
  • Author(s): Hanai Y, Adachi S, Yasuda I, Takai S, Matsushima-Nishiwaki R, Kato H, Enomoto Y, Akamatsu S, Sakakibara S, Ogura S, Iwama T, Kozawa O, Tokuda H.
  • Journal Title: Life Sci. 85 Pages: 386-394
  • Peer Reviewed
• [Journal Article] αB-crystallin extracellularly suppresses ADP-induced granule secretion from buman platelets. (2009)
  • Author(s): Enomoto Y, Tokuda H, et al.
  • Journal Title: FEBS Lett. 583 Pages: 2464-2468
  • Peer Reviewed
• [Journal Article] Antithrombin III suppresses ADP-induced platelet granule secretion : inhibition of HSP27 phosphorylation. (2009)
  • Author(s): Doi T, Tokuda H, et al.
  • Journal Title: Arch.Biochem.Biophys. 489 Pages: 62-67
  • Peer Reviewed
• [Journal Article] A case of raloxifene-induced acceleration of platelet aggregation. (2008)
  • Author(s): Minamitani C, Takai S, Matsushima-Nishiwaki R, Hanai Y, Otsuka T, Kozawa O, Tokuda H.
  • Journal Title: Internal Med. 47 Pages: 1523-1528
  • Peer Reviewed
• [Journal Article] HSP27 phosphorylation is correlated with ADP-induced platelet granule secretion. (2008)
  • Author(s): Kato H, Takai S, Matsushima-Nishiwaki R, Adachi S, Minamitani C, Otsuka T, Tokuda H, Akamatsu S, Doi T, Ogura S, Kozawa O.
  • Journal Title: Arch.Biochem.Biophys. 475 Pages: 80-86
  • Peer Reviewed
• [Journal Article] Involvement of Rho-kinase in sphingosine 1-phosphate-stimulated HSP27 induction in osteoblasts. (2008)
  • Author(s): Minamitani C, Tokuda H, et al.
  • Journal Title: Int. J. Mol. Med. (in press)
  • NAID: 120006340793
  • Peer Reviewed
• [Journal Article] cAMP regulates ADP-induced HSP27 phosphorylation in human platelets.
  • Author(s): Enomoto Y, Adachi S, Doi T, Natsume H, Kato K, Matsushima-Nishiwaki R, Akamatsu S, Tokuda H, Yoshimura S, Otsuka T, Ogura S, Kozawa O, Iwama T.
  • Journal Title: Int.J.Mol.Med. in press
  • NAID: 120006341953
  • Peer Reviewed
• [Presentation] アンチトロンビン皿の血小板に対する抗炎症作用の解析 (2011)
  • Author(s): 土井智章、小澤修、加藤久晶、足立政治、小倉真治
  • Organizer: 第38回日本集中治療医学会学術集会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2011-02-26
• [Presentation] Analysis of new molecular mechanisms and the anti-inflammatory effects of antithrombin III in human platelets. (2010)
  • Author(s): Tomoaki Doi, Seiji Adachi, Hisaaki Kato, Osamu Kozawa, Shinji Ogura
  • Organizer: Thirty-Third Annual Conference on Shock
  • Place of Presentation: Portland, Oregon, U.S.A.
  • Year and Date: 2010-06-13
• [Presentation] アンチトロンビンIIIの新たな分子作用機序の解析:抗炎症作用 (2009)
  • Author(s): 土井智章、小澤修、加藤久品、足立政治、小倉真治
  • Organizer: 第24回日本shock学会総会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2009-05-30
• [Remarks] ホームページ等
• [Remarks]
  • URL: http://www.med.gifu-u.ac.jp/pharma/index.htm
• [Remarks]
  • URL: http://www.med.gifu-u.ac.jp/pharma/index.htm
• [Remarks]
  • URL: http://www.med.gifu.u.ac.jp/pharma/index.htm