| Project/Area Number |
10557223
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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 |
Biological pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
MIWA Masao Pharmaceutical Sciences Professor, 薬学部, 教授 (10046287)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Machiko Pharmaceutical Sciences Research Assistant, 薬学部, 助手 (50137072)
MAEDA Toshio Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (00137069)
SUGATANI Junko Pharmaceutical Sciences Assistant Professor, 薬学部, 講師 (30098131)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | PAF / PAF acetylhydrolase / genetic disposition / renal failure / arteriosclerosis obliterans / oxidized phospholipid / PAF・アセチルヒドロラーゼ / PAFアセチルヒドロラーゼ |
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| Research Abstract |
Platelet-activation factor (RAF) acetylhydrolase (PAF-AH) catalyzes the hydrolysis of the acetyl ester bond at the sn-2 position of PAF to yield biologically inactive lyso-PAF. Serum/plasma PAF-AH is considered to be indispensable for control of the level of circulating PAF, which exhibits a wide spectrum of biological activity at very low concentrations (in the range of 10ィイD1-10ィエD1 to 10ィイD1-11ィエD1 M) in diverse pathophysiological processes. We have found Japanese subjects with PAF-AH deficiency, and have reported that the deficiency or low activity of serum PAF-AH appears to cause more severe symptoms. Whereas Tjoelker et al. have cloned the plasma PAF-AH (46 kDa) cDNA, we purified major plasma PAF-AH enzyme consisting of a 34 kDa protein and about 9 kDa asparagine-conjugated sugar chain(s) from 301 human plasma (Ref. 2). We are in the process of determining the NHィイD22ィエD2 terminus of major PAFA-AH purified from 501 human plasma. Furthermore, we elucidated that the PAF-AH (46 kDa) gene mutation is likely to have a disease relapse in Japanese childhood steroid-responsive nephrotic syndrome (Ref. 3) and cause more severe symptoms in Japanese childhood IgA nephropathy (Ref. 5). Additional experiments, that isolated LDL from the PAF-AH-deficient subjects was more susceptible to oxidation and stimulated adhesion molecule synthesis in endothelial cells (Refs. 4, 6 and 9), indicated that the PAF-AH gene mutation is considered to be become a risk factor in the development of atherosclerotic disease in Japan.
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