Regulation of vascular tone by gaseous mediators ; Interactions of multiple gas-transducing systems

• Project/Area Number: 19500329
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Keio University
• Principal Investigator: KAJIMURA Mayumi Keio University, 医学部, 講師 (10327497)
• Co-Investigator(Kenkyū-buntansha): ISHIKAWA Mami 自治医科大学, 医学部, 講師 (60212859)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 脳血流代謝カップリング / 一酸化炭素 / 硫化水素 / ガスバイオロジー / carbon monoxide / nitric oxide / hydorgen sulfide / cortical microcirculation / cystathionine beta synthase

Research Abstract

ガス分子を生成する酵素系や受容系の多くは、他のガス生成反応と拮抗あるいは共役している例が多数存在するにもかかわらず、その生物学的・病態生理学的意義の探究はほとんどなされていない。本研究の目的は、中枢神経系(CNS)で産生される低分子ガス状メディエータの生成・受容機構を探究し、ガス分子による脳局所血流調節のメカニズムを解明することである。最近NOやCOのみならず、生体内でcysteineの分解にともなって生成される硫化水素(H_2S)が神経伝達や血管弛緩に関わる新しい分子として注目されている。そこでsGCやNOS以外のCOの標的分子の候補蛋白としてH_2S産生酵素であるcystathionineβ-synthase(CBS)に着目し、ガス状メディエータを介した情報伝達制御機構の解明を目指した。第一に、肝組織のメタボローム解析の結果から一酸化炭素(CO)がtranssulfuration pathwayを抑制することに着目し、この代謝系の律速酵素であるCBSの活性がCOにより阻害され、NOでは阻害されないCO特異的な受容体であることを見出した。

Research Products

• [Journal Article] Cystathionine -synthase as a CO-sensitive regulator of bile excretion (2009)
  • Author(s): Shintani T., Iwabuchi T., Soga T., Kato Y., Yamamoto T., Takano N., Hishiki T., Ueno Y., Ikeda S., Sakuragawa T., Ishikawa K., Goda N., Kitagawa Y., Kajimura M., Matsumoto K., and Suematsu M.
  • Journal Title: Hepatology 49 Pages: 141-150
  • Peer Reviewed
• [Journal Article] Platelet and leukocyte adhesion in the microvasculature at the cerebral surface immediately after subarachnoid hemorrhage (2009)
  • Author(s): Ishikawa M, Kusaka G, Yamaguchi N, Sekizuka E, Nakadate H, Minamitani H, Shinoda S, and Watanabe E.
  • Journal Title: Neurosurgery 64 Pages: 546-553
  • Peer Reviewed
• [Journal Article] Cystathionine β-synthase as a CO-sensitive regulator of bile excretion (2009)
  • Author(s): Shintani T., Iwabuchi T., Soga T., Kato Y., Yamamoto T., Takano N., Hishiki T., Ueno Y, Ikeda S., Sakuragawa T., Ishikawa K., Goda N., Kitagawa Y., Kajimura M., Matsumoto K., Suematsu M.
  • Journal Title: Hepatology 292 Pages: 141-150
  • Peer Reviewed
• [Journal Article] The effects of cilostazol on tissue oxygenation upon an ischemic-reperfusion injury in the mouse cerebrum (2009)
  • Author(s): Morikawa T., Hattori K., Kajimura M., Suematsu M.
  • Journal Title: Advances in Experimental Medicine and Biology (In press)
  • Peer Reviewed
• [Journal Article] Blood cell-derived RANTES mediates cerebral microvascular dysfunction, inflammation, and tissue injury after focal ischemia-reperfusion (2008)
  • Author(s): Terao S, Yilmaz G, Stokes KY, Russell J, Ishikawa M, Kawase T, Granger DN
  • Journal Title: Stroke 39 Pages: 2560-2570
  • Peer Reviewed
• [Journal Article] Inflammatory and injury responses to ischemic stroke in obese mice (2008)
  • Author(s): Terao S, Yilmaz G, Stokes KY, Ishikawa M, Kawase T, Granger DN.
  • Journal Title: Stroke 39 Pages: 943-950
  • Peer Reviewed
• [Journal Article] Three-dimensional imaging of growing thrombus in vivo (2008)
  • Author(s): Morikawa T., Kajimura M., Ichikawa M., and Suematsu M.
  • Journal Title: Microvascular Reviews and Communications 2 Pages: 8-12
  • NAID: 130004942918
  • Peer Reviewed
• [Journal Article] Three-dimensional imaging of growing thrombus in vivo (2008)
  • Author(s): Morikawa T., Kajimura M., lchikawa M., Suematsu M.
  • Journal Title: Microvascular Reviews and Communications 2 Pages: 8-12
  • NAID: 130004942918
  • Peer Reviewed
• [Journal Article] Three-dimensional imaging of growing thrombus in vivo (2008)
  • Author(s): Morikawa T., Kajimura M., lchikawa M., Suematsu M.
  • Journal Title: Microvascular Reviews and Communications (In press)
  • NAID: 130004942918
  • Peer Reviewed
• [Journal Article] Real time imaging of mechanically injured-femoral artery in mouse revealed a biphasic pattern of leukocyte accumulation (2007)
  • Author(s): Osaka M., Hagita S., Haraguchi M., Kajimura M., Suematsu M., and Yoshida M.
  • Journal Title: American Journal of Physiology : Heart and Circulatory Physiology 292 Pages: 1876-1882
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1 receptor signaling contributes to platelet-leukocyte-endothelial cell interactions in the cerebral microvasculature (2007)
  • Author(s): Ishikawa M, Sekizuka E, Yamaguchi N, Nakadate H, Terao S, Granger DN, and Minamitani H.
  • Journal Title: Am J Physiol Heart Circ Physiol 292 : 315 Pages: 2306-2315
  • Peer Reviewed
• [Journal Article] Real time imaging of mechanically injured-femoral artery in mouse revealed a biphasic pattem of leukocyte accumulation (2007)
  • Author(s): Osaka M., Hagita S., Haraguchi M., Kajimura M., Suematsu M., Yoshida M.
  • Journal Title: American Journal of Physiology: Heart and Circulatory Physiology 292
  • Peer Reviewed
• [Journal Article] The effects of cilostazol on tissue oxygenation upon an ischemic-reperfusion injury in the mouse cerebrum
  • Author(s): Morikawa T., Hattori K., Kajimura M., and Suematsu M.
  • Journal Title: Advances in Experimental Medicine and Biology (in press)
  • Peer Reviewed
• [Presentation] Blood Brain Barrier KI-KEIO G-COE joint meeting at Karolinska Institute, Stockholm, Sweden(invited speaker) (2009)
  • Author(s): Kajimura M., Hattori K., and Suematsu M.
  • Organizer: Regulation of vascular tone by gaseous mediators ; Interactions of multiple gas-transducing systems
  • Year and Date: 2009-03-24
• [Presentation] 第34回日本微小循環学会 (2009)
  • Author(s): Takayuki Morikawa, Katsuji Hattori, Mayumi Kajimura, and Makoto Suematsu
  • Organizer: Carbon monoxide as a tonic modulator against hydrogen sulfide-dependent vasodilatation in the murine cerebellar microcirculation
  • Place of Presentation: 東京
  • Year and Date: 2009-02-20
• [Presentation] Carbon monoxide as a tonic modulator against hydrogen sulfide-dependent vasodilat ation in the murine cerebellar microcirculation (2009)
  • Author(s): 森川 隆之, 服部 克次, 梶村 眞弓, 末松 誠
  • Organizer: 第34回日本微小循環学会
  • Place of Presentation: 東京
  • Year and Date: 2009-02-20
• [Presentation] The 81^<th> Annual Meeting of the Japanese Biochemical Society (2008)
  • Author(s): Kuga K, Mandai S, Kajimura M, Suematsu M, Takeoka S
  • Organizer: Effect of poly(ethylene glycol)-modified albumin on blood components
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2008-12-11
• [Presentation] Effect of poly(ethylene glycol)-modified albumin on blood components. (2008)
  • Author(s): Kuga K, Mandai s, Kajimura M, Suematsu M, Takeoka s.
  • Organizer: The81^<th> Annual Meeting of the Japanese Biochemical Society
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2008-11-10
• [Presentation] Morikawa T., Hattori K., Kajimura M., and Suematsu M. (2008)
  • Author(s): International Society on Oxygen Transport to Tissue
  • Organizer: The effects of cilostazol on tissue oxygenation upon an ischemicreperfusion injury in the mouse cerebrum
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2008-08-06
• [Presentation] The effects of cilostazol on tissue oxygenation upon an ischemic-reperfusion injury in the mouse cerebrum. (2008)
  • Author(s): Morikawa T., Hattori K., Kajimura M., Suematsu M.
  • Organizer: The36^<th> International Society on Oxygen Transport to Tissue
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2008-08-05
• [Presentation] International Society on Oxygen Transport to Tissue (2008)
  • Author(s): Kajimura M., Hattori K., Morikawa K., Ishikawa M., and Suematsu M.
  • Organizer: Regulation of vascular tone by gaseous mediators ; Interactions of multiple gas-transducing systems utilizing molecular oxygen (invited speaker)
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2008-08-04
• [Presentation] Regulation of vascular tone by gaseous mediators ; Interactions of multiple gas-transd ucing systems utilizing molecular oxygen (2008)
  • Author(s): Kajimura M., Hattori K., Morikawa K., Ishikawa M., Suematsu M.
  • Organizer: The36^<th> International Society on Oxygen Transport to Tissue
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2008-08-04
• [Presentation] 第31回日本バイオレオロジー学会(シンポジスト) (2008)
  • Author(s): 梶村 眞弓、石川 眞実、末松誠
  • Organizer: 低分子ガスを介した情報伝達系による脳微小循環機能制御機構
  • Place of Presentation: 東京
  • Year and Date: 2008-06-06
• [Presentation] 低分子ガスを介した情報伝達系による脳微小循環機能制御機構 (2008)
  • Author(s): 梶村 眞弓
  • Organizer: 第31回日本バイオレオロジー学会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-06
• [Presentation] Vascular Response to Injury "UC Davis-KEIO G-COE joint meeting at University of California, Davis, U.S.A. (2008)
  • Author(s): Kajimura M., Hattori K., and Suematsu M.
  • Organizer: Multiple gaseous transducing systems
  • Place of Presentation: invited speaker
  • Year and Date: 2008-04-10
• [Presentation] Distinct effects of cilostazol and aspirin on thromboembolic reation and microvascular permeability (2007)
  • Author(s): Morikawa T. Kajimura M., Ichikawa M., Hoshino R., Suematsu M.
  • Organizer: The 80th Annual Meeting of the Japanese Biochemical Society
  • Place of Presentation: Yokohama
  • Year and Date: 2007-12-16
• [Presentation] The 80^<th> Annual Meeting of the Japanese Biochemical Society (2007)
  • Author(s): Yokohama, Japan. Morikawa T. Kajimura M., Ichikawa M., Hoshino R., Suematsu M.
  • Organizer: Distinct effects of cilostazol and aspirin on thromboembolic reation and microvascular permeability
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2007-12-12
• [Presentation] The 8^<th> World Congress for Microcirculation (2007)
  • Author(s): Mandai S. Kajimura M., Morikawa T. Tsukada K., Mochizuki Y., Takeoka S., Nakajou K., and Suematsu M.
  • Organizer: Effects of polyethylene-glycol-modified human recombinant albumin on hemostasis
  • Place of Presentation: Wisconsin, USA
  • Year and Date: 2007-08-18
• [Presentation] Effects of polyethylene-glycol-modified human recombinant albumin on hemostasis (2007)
  • Author(s): Mandai S. Kajimura M., Morikawa T. Tsukada K., Mochizuki Y., Takeoka s., Nakajou K., Suematsu M.
  • Organizer: The 8th World Congress for Microcirculation
  • Place of Presentation: Milwaukee,Wisconsin
  • Year and Date: 2007-08-17
• [Presentation] The 8^<th> World Congress for Microcirculation, Milwaukee (2007)
  • Author(s): Wisconsin. Kajimura M.
  • Organizer: Interactions of multiple-gas transducing systems in the brain microcirculation
  • Place of Presentation: invited speaker
  • Year and Date: 2007-08-16
• [Presentation] Interactions of multiple-gas transducing systems in the brain microcirculation (2007)
  • Author(s): Kajimura M.
  • Organizer: The 8th world congress for Microcirculation
  • Place of Presentation: Milwaukee,Wisconsin
  • Year and Date: 2007-08-16
• [Presentation] 第28回日本炎症再生医学会 (2007)
  • Author(s): 森川隆之、梶村眞弓、木村美緒、星野利津子、末松誠
  • Organizer: 止血血栓形成プロセス及び血管透過性に及ぼすcilostazolの効果-aspirinとの比較-
  • Place of Presentation: 東京
  • Year and Date: 2007-08-03
• [Presentation] 止血血栓形成プロセス及び血管透過性に及ぼすcilostazolの効果-aspirinとの比較 (2007)
  • Author(s): 森川 隆之、梶村 真弓、木村 美緒、星野 利津子、末松 誠
  • Organizer: 第32回日本炎症再生学会
  • Place of Presentation: 東京
  • Year and Date: 2007-07-16
• [Book] 一酸化炭素とシグナル伝達吉川敏一監修酸化ストレスの医学 (2008)
  • Author(s): 山本雄広、高野直治、梶村眞弓、足立健、末松誠
  • Publisher: 診断と治療社