| Project/Area Number |
12557008
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General pharmacology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TAMAKI Toshiaki The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (80179879)
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| 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)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| 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)
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| Keywords | ET-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 |
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| 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.
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