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Pathophysiological role of ET-1(1-31) on the inflammatory diseases.

Research Project

Project/Area Number 12557008
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General pharmacology
Research InstitutionThe University of Tokushima

Principal Investigator

TAMAKI Toshiaki  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (80179879)

Co-Investigator(Kenkyū-buntansha) HIROSE Masaru  Naruto university of education, Health Service Center, Professor, 保健管理センター, 教授 (90183582)
YOSHIZUMI Masanori  The University of Tokushima, School of Medicine, Assistant Professor, 医学部, 講師 (60294667)
KIDO Hiroshi  The University of Tokushima, The institute for molecular enzyme research, Professor, 分子酵素学研究センター, 教授 (50144978)
TSUCHIYA Koichiro  The University of Tokushima, School of Medicine, Lecturer, 医学部, 助手 (70301314)
NISHIKIBE Masaru  Banyu Pharmaceutical, Tsukuba research institute of Banyu Pharmaceutical, Pharmacology Development Research Laboratories, Director, 萬有製薬つくば研究所, 薬理研究所(研究職)
錦邉 優  萬有製薬, 萬有製薬つくば研究所, 薬理研究所長(研究職)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥5,000,000 (Direct Cost: ¥5,000,000)
KeywordsET-1(1-31) / Monocyte / Mesangium cell / MCP-1 / Reactive oxygen species / Electron paramagnetic resonance / JNK / AP-1 / Endothelin-1(1-31) / mesangium cell / glomerulus / p38MAP kinase / antioxidants / chemotactic effect / monocyte / human mesangial cell / MAP kinase / ERK / p38 MAP kinase / chemotaxis / neutrophil
Research Abstract

1) ET- 1(1-31) exhibited chemotactic activities toward human neutrophils and monocytes as an inflammatory mrdiator. The chemotactic effects induced by ET-1(1-31) was inhibited by BQ123, an ET_A receptor antagonist, but not by BQ788, an ET_B receptor antagonist.
2) ET-1(1-31) directly cause the migration of mesangial cells and may be responsible for recruitment of mononuclear cells mediated through the mesangial cell activation. Since human cymase has been reported to be involved in glomerular disease, ET-1 (1-31) may be one of the mediators.
3) ET-1(1-31) caused a significant increase in the electron paramagnetic resonance signal of the DMPO/OH radical spin adduct in rat aortic smooth muscle cells(RASMC). Antioxidants inhibit ET-1(1-31)-induced RASMC proliferation by inhibiting reactive oxygen species. The underlying mechanisms of the inhibition of cellular proliferation by antioxidants may be explained, in part, by the inhibition of JNK activation and the resultant inhibition of AP-1-DNA binding.
4) Before surgery in patients with abdominal aortic aneurysma, plasma concentrations of ET-1(1-31) were higher than those in healthy individuals. After surgery, ET-1(1-31) in plasma decreased to the levels similar to those of healthy subjects.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] M.Yoshizumi: "Effect of endothelin-1(1-31) on the human mesangial cell proliferation"Jap.J.Pharmaclo.. 84. 146-155 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] D.Inui: "Effect of endothelin-1(1-31) on p38 mitogen-activated protein kinase in cultured human mesangial cells"Life Sciences. 68. 635-645 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Okishima: "Determination of the levels of novel 31-amino acid endothelins and endothelins in human lungs"Life Sciences. 68. 2073-2080 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] P.Cui: "A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes"J.Leukocyte Biology. 70. 306-312 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Moe Kyaw: "Antioxidants inhibit endothelin-1(1-31)-induced proliferation of vascular smooth muscle cells via the inhibition of mitogen-activated protein (MAP) kinase and activator protein-1(AP-1)"Biochemical Pharmacology. 64. 1521-1531 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Suzaki: "Determination of plasma concentrations of endothelin-1(1-3 1) and endothelin-1 in healthy subjects and patients with atherosclerosis"J.Cardiovasc.Pharmacol.. 41(suppl.1). S83-S87 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Yoshizumi, S. Kagami, Y. Suzaki, K. Tsuchiya, H. Houchi, T. Hisayama, H. Fukui, T. Tamaki: "Effect of endothelin-1(1-31) on the human mesangial cell proliferation."Jap. J. Pharmaclo.. 84. 146-155 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] D. Inui, M. Yoshizumi, Y. Suzaki, K. Kirima, K. Tsuchiya, H. Houchi, S. Kagami, and T. Tamaki: "Effect of endothelin-1(1-31) on p38 mitogen-activated protein kinase in cultured human mesangial cells."Life Sciences. 68. 635-645 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Okishima, M. Yoshizumi, K. Tsuchiya, P. Cui, H. Kitamura, T. Tamaki, H. Kido: "Determination of the levels of novel 31-amino acid endothelins and endothelins in human lungs."Life Sciences. 68. 2073-2080 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] P. Cui, K. Tani, H. Kitamura, Y. Okumura, M. Yano, D. Inui, T. Tamaki, S. Sone, H. Kido: "A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes."J. Leukocyte Biology. 70. 306-312 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Yoshizumi, K. Tsuchiya, K. Kirima, Moe Kyaw, Y. Suzaki, T. Tamaki: "Quercetin inhibits Shc- and Phosphatidylinositol 3-kinase-mediated c Jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells."Molecular Pharmacology. 60. 656-665 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Suzaki, M. Yoshizumi, S. Kagami, AH. Koyama, Y Taketani, H. Houchi, K. Tsuchiya, E. Takeda and T. Tamaki: "Hydrogen peroxide stimulates c-Src-mediated big mitogen-activated protein kinase 1 (BMK1) and the MEF2C signaling pathway in PC12 cells. Potential role in cell survival following oxidative insults."J. Biol. Chem.. 277. 9614-9621 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Moe Kyaw, M. Yoshizumi, K. Tsuchiya, K. Kirima, Y. Suzaki, S. Abe, T. Hasegawa, T. Tamaki: "Antioxidants inhibit endothelin-1(1-31)-induced proliferation of vascular smooth muscle cells via the inhibition of mitogen-activated protein (MAP) kinase and activator protein-1 (AP-1)."Biochemical Pharmacology. 64. 1521-1531 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Yoshizumi, K. Tsuchiya, Y. Suzaki, K. Kirima, Moe Kyaw, JH. Moon, J. Terao and T. Tamaki.: "Quercetin Glucronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway."Biochemical and Biophysical Research Communications. 293. 1458-1465 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Suzaki, M. Yoshizumi, Y. Yamashita, S. Abe, K. Tsuchiya, Y. Satoh, Y. Kuroda, K. Horike, M. Kano, Y. Fukuta, T. Kitaichi, T. Hori, Y. Masuda, T. Kitagawa, K. Minakuchi, and T. Tamaki: "Determination of plasma concentrations of endothelin-1(1-31) and endothelin-1 in healthy subjects and patients with atherosclerosis."J. Cardiovasc. Pharmacol.. 41. S83-S87 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Ozawa, T. Hasegawa, K. Tsuchiya, M. Yoshizumi, T. Tamaki: "Effect of endothelin-1(1-31) on the renal resistance vessels."J. Medical Investigation. 525. 87-94 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Moe Kyaw: "Antioxidants inhibit endothelin-1(1-31)-induced proliferation of vascular smooth muscle cells via the inhibition of mitogen-activated protein (MAP) kinase and activator protein-1 (AP-1)"Biochemical Pharmacology. 64. 1521-1531 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akiko Kitamura: "Endothelin-1 is a potent stimulator of α1β1 integrin-mediated collagen matrix remodeling by rat mesangial cells"Biochem. Biophys. Res. Commun.. 299. 555-561 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yuki Suzaki: "Hydrogen peroxide stimulates c-Src-mediated big mitogen-activated protein kinase 1 (BMK1) and the MEF2C signaling pathway in PC12 cells. Potential role in cell survival following oxidative insults"J. Biol. Chem.. 277. 9614-9621 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masanori Yoshizumi: "Quercetin Glucronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway"Biochemical and Biophysical Research Communications. 293. 1458-1465 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masanori Yoshizumi: "Ebselen attenuates oxidative styress-induced apoptosis via the inhibition of the c jun N-terminal kinase and activator protein-1 signaling pathway in PC12 cells"Br. J. Pharmacology. 136. 1023-1032 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Naoko Okishima: "Determination of the levels of novel 31-amino acid endothelins and endothelins in human lungs"Life Sciences. 68. 2073-2080 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masanori Yoshizumi: "Signal transduction of reactive oxygen species and mitogenactivated protein kinaases in cardiovascular disease"J. Med Invest. 48. 11-24 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masanori Yoshizumi: "Quercetin inhibits Shc-and Phosphatidylinositol 3-kinase-mediated JNK activation by angiotensin II in culture rat aortic smooth muscle cells"Molecular Pharmacology. 60. 656-665 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Pig Cui: "A novel bioactive 31-amino acid endothelin-1 is a potent chemotactic peptide for human neutrophils and monocytes"J. Leukocyte Biology. 70. 306-312 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masanori Yoshizumi: "Src and Cas mediate JAK Activation but Not ERk1/2 and p38 Kinases by Reactive Oxygen Species"The Journal of Biological Chemistry. 275・16. 11706-11712 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masanori Yoshizumi: "Effect of Endothelin-1(1-31) on Human Mesangial Cell Proliferation"The Japanes Journal of Pharmacology. 84・. 145-155 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Daisuke Inui: "Effect of endothelin-1(1-31) on p38 mitogen-activated protein kinase in cultured human mesangial cells"Life Sciences. 68・. 635-645 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉栖正典: "エンドセリン-1(1-31)の腎作用"腎と透析. 49・4. 739-743 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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