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Development of the method(s) to monitor cardiovascular function and its intracellular signal transduction

Research Project

Project/Area Number 09557005
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General physiology
Research InstitutionYamaguchi University

Principal Investigator

KOBAYASHI Sei  Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (80225515)

Co-Investigator(Kenkyū-buntansha) KODAMA Yuka  Carl Zeiss, Microscopy Department, Researcher, 研究員
TODOROKI Natsuko  Yamaguchi University, School of Medicine, Research Associate,, 医学部, 助手 (90253153)
MOGAMI Kimiko  Yamaguchi University, School of Medicine, Research Associate, 医学部, 助手 (80263771)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥10,600,000 (Direct Cost: ¥10,600,000)
KeywordsSignal Transduction / Cytosolic Celcium Ion / Endothelial Cells / Ryo-kinase / Sphingolipids / Vascular Smooth Muscle / 細胞内情報伝達 / 血管手滑筋 / Rho-kinase
Research Abstract

The following results were obtained :
1. FIRST YEAR : We developed the method to monitor cardiovascular function and its intracellular signal transduction. We introduced rapidly recombinant proteins into the cytosol of vascular smooth muscle strips, using the receptor-coupled membrane permeabilization. Using this new system, we identified Rho-kinase as a novel messenger for the CaィイD12+ィエD1-independent contraction of vascular smooth muscle. This conclusion was supported by the following results.
1)Recombinant catalytic domain of Rho-kinase is constitutively active and induced the CaィイD12+ィエD1-independent contraction of permeabilized vascular smooth muscle in the absence of cytosolic GTE. 2) Rho-kanase-induced contraction was associated with the elevation of myosin light chain phosphorylation. 3) Rho-kinase-induced contraction and increase in the myosin light chain phoshorylation were resistant to a myosin light chain kinase blocker.
2. SECOND YEAR : We investigated signal transduction fro … More m the cell membrane to cytosolic messenger (Rho-kinase). We identified several sphingolipids as a novel mediator for the CaィイD12+ィエD1-independent contraction of vascluar smooth muscle. In addition, we found that the sphingolipids induces CaィイD12+ィエD1-independent contraction in the absence of cytosolic GTP in permeabilized vascular smooth muscle strips, which was blocked by a Rho-kinase inhibitor, suggesting that sphingolipid-induced contraction is mediated by Rho-kinase. Fluorometry of fura-2 revealed that sphingolipids induced large contraction without elevation of cytosolic CaィイD12+ィエD1 concentration ([CaィイD12+ィエD1]i) in cerebral arteries, supporting the role of sphingolipid as a mediator for the CaィイD12+ィエD1-independent contraction.
3. THIRD TEAR : We started to investigate the CaィイD12+ィエD1-independent contraction of human vascular smooth muscle strips. Sphingolipid induced very small contraction obtained from patients whose cholesterol levels are normal, but induced large contraction of the strips obtained from patients whose cholesterol levels are high. These finding suggest that a sphingolipid/Rho-kinase pathway plays an important role in the development of abnormal vascular contraction which was frequently associated with hyperlipidemia. Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Kureishi Y: "Pho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation"J.Biol.Chem.. 272. 12257-12260 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawasaki J: "Thg mechanisnii of the relaxation induced by vasoactive intestinal piptide in the porcine coronary artery"Br.J.Pharmacol.. 121. 977-985 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Chen X: "Resting load and modulati6n of the myofilament Ca^<2+> sensitivity in rabbit cerebral arteries"J.Cerebral Blood Flow Metab.. 17. 236-240 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Eguchi D: "Mechanism of contraction induced by bradykinin in the rabbit saphenous vein"Br.J.Pharmacol.. 120. 371-378 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mogami,K.: "Sphingosylphosphorylcholine induces cytosolic Ca^<2+> elevation in endothelial cells in situ and endothelium-dependent relacatio through nitric oxide production in bovine coronary artery"FEBS Lett. 457. 375-380 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishida,K.: "Thiopentone inhibits endothelium-dependent relaxations of rat regulated by endothelial Ca^<2+> -dependent K^+ channels"Eur J Pharmacol. 371. 179-185 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sumiyoshi R: "Diadenosine polyphosphates directly relax porcine coronary arterial smooth muscle"J Pharmacol.Exp.Ther.. 283. 548-556 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Eguchi D: "Down-regulation of endothelin B receptors in autogenous saphenous veins grafted into the arterial circulation"Cardiovas.Res.. 35. 360-367 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishimura J: "The relaxant effect of adrenomedullim on particular smooth muscles despite a general expresion of its mRNA in smooth muscle,endothelial and epithelial cells"Br.J.Pharmacol.. 120. 193-200 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kozai T: "Tyrosine kinase inhibitor markedly suppressed the development of coronary lesions induced by long-term treatment with platelet-derived growth factor in pigs in vivo"Cardiovasc.Pharmacol.. 29. 536-545 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Todoroki-Ikeda N: "Novel mechanisum for increasing Ca^<2+> sensitivity of contractile apparatus in smooth muscle"Masui. 47(5). 530-540 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ahmed A: "Differential effects of Ca^<2+> channel blockers on Ca^<2+> tansients and cell cycle progression in vascular smooth muscle cells"Eur.J.Pharmacol.. 344. 323-331 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kobayashi,S.: "A View Of Smooth Muscle"JAI press lnc.,Greenwich,Connecticut(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] NISHIMURA, J: "The relaxant effect of adrenomedullin on particular smooth muscles despite a general expression of its mRNA in smooth muscle, endothelial and epithelial cells."Br. J. Pharmacol.. 120. 193-200 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] CHEN, X: "Resting load and modulation of the myofilament CaィイD12+ィエD1 sensitivity in rabbit cerebral arteries."J. Cerebral Blood Flow Metab.. 17. 236-240 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] KUREISHI, Y: "Rho-associated kinase directly induces smooth muscle contraction though myosin light chain phosphorylation."J. Boil. Chem.. 272. 12257-12260 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] EGUCHI, D: "Mechanism of contraction induced by bradykinin in the rabbit saphenous vein."Br. J. Pharmacol.. 120. 371-378 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] KAWASAKI, J: "The mechanisms of the relaxation induced by vasoactive intrstinal petide in the porcine coronary artery."Br. J. Pharmacol.. 121. 977-985 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] KOZAI, T: "Tyrosine kinase inhibitor markedly suppressed the development of coronary lesions induced by long-term treatment with platelet-derived growth factor in pigs in vivo."Cardiovasc. Pharmacol.. 29. 536-545 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] EGUCHI, D: "Down-regulation of endothein B receptors in autogenous saphenous veins grafted into the arterial circulation."Cardiovas. Res.. 35. 360-367 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] SUMIYOSHI, R: "Diadenosine polyphosphates directly relax porcine coronary arterial smooth muscle."J. Pharmacol. Exp. Ther.. 283. 548-556 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] YOSHIMURA, H: "Expression and function of endothelins, endothelin receptors, and endothelin converting enzyme in the porcine trachea."Am. J. Respir. Cell Mol. Biol.. 17. 471-480 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] AHMED, A: "Differential effects of CaィイD12+ィエD1 channel blockers on CaィイD12+ィエD1 transients and cell cycle progression in vascular smooth muscle cells."Eur. J. Pharmacol.. 344. 323-331 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] TODOROKI-Ikeda, N: "Novel mechanisms for increasing CaィイD12+ィエD1 sensitivity of contractile apparatus smooth muscle."Masui. 47(5). 530-540 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] MOGAMI, K: "Sphingosylphosphorylcholine induces cytosolic CaィイD12+ィエD1 elevation in endothelial cells in situ and causes endothelium-dependentrelaxation through nitric oxide production in bovine coronary artery."FEBS Lett. 457. 375-380 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] ISHIDA, K: "Thiopentone inhibits endothelium-dependent relaxations of rat aortas regulated by endothrlial CaィイD12+ィエD1-dependent KィイD1+ィエD1 channels."Eur J Pharmacol. 371. 179-185 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] KOBAYASHI, S: "Potential signal mediators for CaィイD12+ィエD1 sensitization of smooth muscle contraction : Rho-associated kinase, atypical protein kinase C, and arachidonic acid."In : A View of Smooth Muscle (Ed. Barr L and Christ G), JAI press Inc., Greenwich, Connecticut. (In Press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mogami,K.: "Sphingosylphosphorylcholine induces cytosolic ca^<2+> elevation in endothelial cells in situ and causes endothelium-dependent relaxation through nitric oxide production in bovine coronary artery."FEBS Lett. 457:. 375-380 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishida,K.: "Thiopentone inhibits endothelium-dependent relaxations of rat aortas regulated by endothelial Ca^<2+> -dependent K^+channels."Eur J Pharmacol. 371:. 179-185 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kobayashi,S.: "A View of Smooth Muscle"JAI press Inc.,Greenwich,Connecticut(印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Ahmed,A.: "Differential effects of Ca^<2+> Channel blockers on Ca^<2+> transients and cell cycle progression in vascular smooth muscle cells." Eur.J.Pharmacol.344. 323-331 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 轟-池田 奈津子: "平滑筋収縮装置のCa^<2+>感受性を増加させる新規の細胞内情報伝達機構." 麻酔. 47(5). 530-540 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kobayashi,S.: "A View of Smooth Muscle (印刷中)" JAI press Inc.,Greenwich,Connecticut,

    • Related Report
      1998 Annual Research Report
  • [Publications] Kureishi Y: "Rho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation." J.Biol.Chem.272. 12257-12260 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawasaki J: "The mechanisms of the relaxation induced by vasoactive intestinal peptide in the porcine coronary artery." Br.J.Pharmacol.121. 977-985 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Chen X: "Resting load and modulation of the myofilament Ca^<2+> sensitivity in rabbit cerebral arteries." J.Cerebral Blood Flow Metab.17. 236-240 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kozai T: "Tyrosine kinase inhibitor markedly suppressed the development of coronary lesions induced by long-term treatment with platelet-derived growth factor in pigs in vivo." J.Cardiovasc. Pharmacol.29. 536-545 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishimura J: "The relaxant effect of adrenomedullin on particular smooth muscles despite a general expression of its mRNA in smooth muscle, endothelial and epithelial cells." Br.J.Pharmacol.120. 193-200 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Eguchi D: "Mechanism of contraction induced by bradykinin in the rabbit saphenous vein." Br.J.Pharmacol.120. 371-378 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kobayashi S: "A View of Smooth Muscle" JAI press Inc. (In Press),

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-11-11  

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