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2002 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 2000 – 2002
KeywordsET-1(1-31) / Monocyte / Mesangium cell / MCP-1 / Reactive oxygen species / Electron paramagnetic resonance / JNK / AP-1
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.

  • Research Products

    (16 results)

All Other

All Publications (16 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
  • [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
  • [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
  • [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
  • [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
  • [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)

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      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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)

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Published: 2004-04-14  

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