Research of developmental engineering of the sphingosine-1-phosphate receptor as a target molecules of antiatherosclerotic drug

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590284
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kanazawa University
• Principal Investigator: OKAMOTO Yasuo 金沢大学, 医学系, 准教授 (80293877)
• Project Period (FY): 2010 – 2012
• Keywords: スフィンゴシン-1-リン酸 / 動脈硬化

Research Abstract

The lysophospholipid mediator sphingosine-1-phosphate (S1P) exerts a facilitative effect on atherosclerosis via S1P2 receptor. In addition, S1P-synthesizing enzyme SphK1 also has a proatherosclerotic effect. These observations suggest the possibility that the lipid mediator S1P signaling could be potential novel therapeutic targets for atherosclerosis.

Research Products

• [Journal Article] Essential role of class II PI3K-C2α in sphingosine-1-phosphate receptor-1 mediated signaling and migration in endothelial cells (2013)
  • Author(s): Biswas K, Yoshioka K, Asanuma K, Okamoto Y, Takuwa N, Sasaki T, TakuwaY
  • Journal Title: J. Biol. Chem Volume: 288 Pages: 2325-2339
  • DOI: DOI:10.1074/jbc.M112.409656
  • Peer Reviewed
• [Journal Article] Essential role of endothelial class II PI3K-C2αin angiogenesis and vascular barrier function (2012)
  • Author(s): Yoshioka K, Yoshida K, Cui H, Wakayama T, Takuwa N, Okamoto Y, Du W, Qi X, Asanuma K, Sugihara K, Aki S, Miyazawa H, Biswas K, Nagakura C, Ueno M, Iseki S, Schwartz JR, Okamoto H, Sasaki T,Matsui O, Asano M, Adams HR, Takakura N, Takuwa Y.
  • Journal Title: Nature med Volume: 18 Pages: 1560-1569
  • DOI: DOI:10.1038/nm.2928
  • Peer Reviewed
• [Journal Article] Intraradial administration of fasudil inhibits augmented Rho kinase activity to effectively dilate spastic radial artery in coronary artery bypass grafting surgery (2011)
  • Author(s): Takagi T, Okamoto Y, Tomita S, Sato A, Yamaguchi S, Takuwa Y, Watanabe G
  • Journal Title: J Thorac Cardiovasc Surg Volume: 142 Pages: 59-65
  • URL: http://dx.doi.org/10.1016/j.jtcvs.2011.01.055
  • Peer Reviewed
• [Journal Article] Sphingosine-1-Phosphate-Specific G Protein-Coupled Receptors as Novel Therapeutic Targets for Atherosclerosis Pharmaceuticals (2011)
  • Author(s): Okamoto Y, Wang F, Yoshioka K, Takuwa N, Takuwa Y
  • Volume: 4
  • Pages: 117-137
  • Peer Reviewed
• [Journal Article] スフィンゴシン-1-リン酸シグナル伝達系の新血管系における機能 (2011)
  • Author(s): 岡本安雄,吉岡和晃,多久和典子,多久和陽
  • Journal Title: 生化学 Volume: 8 Pages: 536-544
  • URL: http://www.jbsoc.or.jp/event/magazine/pdf/83-06-10.pdf
  • Peer Reviewed
• [Journal Article] Enhanced Ca2+-Dependent Activation of PI3K class IIα isoform-Rho Axis in Blood Vessels of Spontaneously Hypertensive Rats (2010)
  • Author(s): Seok YM, Azam MA, Okamoto Y, Sato A, Yoshioka K, Maeda M, Kim IK, Takuwa Y
  • Journal Title: Hypertension Volume: 56 Pages: 934-941
  • DOI: DOI:10.1161/HYPERTENSIONAHA.110.160853
  • Peer Reviewed
• [Journal Article] Sustained delivery of sphingosine-1-phosphate usingpoly(lactic-co-glycolic acid)-based microparticles stimulatesAkt/ERK-eNOS mediated angiogenesis and vascular maturation restoringblood flow in ischemic limbs of mice (2010)
  • Author(s): Qi X, Okamoto Y, Murakawa T, Wang F, Oyama O, Ohkawa R, Yoshioka K, Du W,Sugimoto N, Yatomi Y, Takuwa N, Takuwa Y.
  • Journal Title: Eur J Pharmacol Volume: 63 Pages: 121-131
  • DOI: DOI:10.1016/j.ejphar.2010.02.038
  • Peer Reviewed
• [Journal Article] the G protein-coupled receptor for sphingosine-1-phosphate, negativelyregulates tumor angiogenesis and tumor growth in vivo in mice (2010)
  • Author(s): Du W, Takuwa N, Yoshioka K, Okamoto Y,Gonda K, Sugihara K, Fukamizu A, Asano M, Takuwa Y
  • Journal Title: CancerRes. Volume: 70 Pages: 772-781
  • DOI: DOI:10.1158/0008-5472.CAN-09-2722
  • Peer Reviewed
• [Journal Article] S1P3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species (2010)
  • Author(s): Takuwa N, Ohkura S, Takashima S, Ohtani K, Okamoto Y, Tanaka T, Hirano K, Usui S, Wang F, Du W, Yoshioka K, Banno Y, Sasaki M, Ichi I, Okamura M, Sugimoto N, Mizugishi K, Nakanuma Y, Ishii I, Takamura M, Kaneko S, Kojo S, Satouchi K, Mitumori K, Chun J, Takuwa
  • Journal Title: Cardiovasc Res Volume: 85 Pages: 484-493
  • DOI: DOI:10.1093/cvr/cvp312
  • Peer Reviewed
• [Presentation] スフィンゴシン1-リン酸特異的2 型受容体は内皮型一酸化窒素合成酵素を抑制することによりアナフィラキシーショックに対して保護的に働く (2013)
  • Author(s): 崔弘,岡本安雄,吉岡和晃,杜娃,多久和典子,張威,Kuntal Biswas,安藝翔,趙〓〓,九田裕一,浅野雅秀,芝本利重,多久和陽
  • Organizer: 第90回日本生理学会
  • Place of Presentation: タワーホール船堀(東京都)
  • Year and Date: 2013-03-27
• [Presentation] Function role of sphingosine-1-phosphate signaling in angiogenesis (2011)
  • Author(s): Yasuo Okamoto, Xun Qi, Wa Du, Noriko Takuwa, kazuaki Yoshioka, Yoh Takuwa
  • Organizer: The 1stAsia-Pacific Vascular Biology Meeting and 第19回日本血管生物医学会学術集会
  • Place of Presentation: 東京ステーションコンファレ
  • Year and Date: 2011-12-09
• [Presentation] ポリ乳酸-グリコール酸共重合体を基材としたスフィンゴシン-1-リン酸徐放微粒子製剤による持続性放出はマウス虚血肢においてAkt/ERK-eNOSを介して血管新生および血管成熟を促進し血流を回復させる (2011)
  • Author(s): 戚 〓,岡本安雄,吉岡和晃,王飛,崔弘,Biswas Kuntal,安藝翔,Dandar Erdembileg,多久和典子,多久和陽
  • Organizer: 日本分子生物学会第11回春季シンポジウム
  • Place of Presentation: 石川県立音楽堂(石川県金沢市)
  • Year and Date: 2011-05-26
• [Presentation] 自然発症高血圧ラットにおける血管のCa2+依存性PI3KC2α-Rho経路の役割 (2010)
  • Author(s): 岡本安雄,石英美,アザムモハメドアリ,佐藤篤志,吉岡和晃,王飛,崔弘,多久和典子,多久和陽
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡市民文化ホール・いわて県民情報交流センター(岩手県盛岡市)
  • Year and Date: 2010-05-21
• [Book] 脂質メディエーター (2011)
  • Author(s): 岡本安雄
  • Total Pages: 420-421
  • Publisher: 朝倉書店
• [Remarks]
  • URL: http://physiology1.w3.kanazawa-u.ac.jp/
• [Patent(Industrial Property Rights)] 血管内皮関門障害に関連した疾患又は症状を予防及び/又は治療するための候補物質のスクリーニング方法 (2013)
  • Inventor(s): 多久和陽,岡本安雄
  • Industrial Property Rights Holder: 多久和陽,岡本安雄
  • Industrial Property Number: 特願2013-033893
  • Filing Date: 2013-02-22