| Project/Area Number |
02454257
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
YOKOYAMA Mitsuhiro Kobe University School of Medicine Professor, 医学部, 教授 (40135794)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIOKA Yoshio Kobe University School of Medicine Hospital Clinical Fellow, 医学部附属病院, 医員
INOUE Nobutaka Kobe University School of Medicine Hospital Clinical Fellow, 医学部附属病院, 医員 (10304099)
KAWAHARA Yasuhiro Kobe University School of Medicine Hospital Assistant Professor, 医学部附属病院, 講師 (80169755)
AKITA Hozuka Kobe University School of Medicine Hospital Assistant Professor, 医学部附属病院, 講師 (60175792)
ISHIKAWA Yuichi Kobe University School of Medicine Associate Professor, 医学部, 助教授 (90159707)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1991: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1990: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | endothelial cell / endothelium-derived relaxing factor / phosphatidyl inositol tunover / cytosolic calcium / lysophosphatidylcholine / oxidized LDL / HDL / signal transduction system / 酸化低比重リポ蛋白質 / 血管平滑筋 |
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| Research Abstract |
1. The mechanism of production and release of endothelium-derived relaxing factor (EDRF) in vascular endothelial cells
We measured both phosphatidyl inositol turnover and cytosolic calcium concentration in cultured bovine aortic endothelial cells. Bradykinin induced phosphatidyl inositol (PI) turnover and calcium release from intracellular store and influx of extracellular calcium in dose-dependent manners. We proved that EDRF was produced and released through this signal transduction system using bioassay method. Furthermore the investigation of this signal transduction system is now in proatess usincy measurement of nitric oxide, which is thought to be EDRF, with chemiluminescence mehtod.
2. Effects of lysophospholipids and modified lipoproteins on the production and release of EDRF
(1) We reported that oxidized low density lipoprotein (ox-LDL) inhibits the vasodilatation induced by EDRF which is released after agonist stimulation and that it is due to increased lysophosphatidylcholine (LPC) in ox-LDL. We demonstrated that in cultured endothelial cells, both ox-LDL and LPC inhibited PI turnover and elevation of cytosolic calcium induced by Bradykinin in dose-dependent manners. It was concluded that the inhibition of this signal transduction system is one of the mechanisms by which ox-LDL inhibits EDRF production or release.
(2) We found that high density lipoprotein (HDL) and native LDL reduced the inhibitory effects of ox-LDL on EDRF production or release and that it was due to prevention of LPC transfer from ox-LDL to endothelial cells and removal of transferred LPC from endothelial ceIls.
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