| Project/Area Number |
04404081
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | University of Tokyo |
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Principal Investigator |
INOUE Keizo Univ.of Tokyo, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30072937)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Junken Univ.of Tokyo, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (20250219)
ARAI Hiroyuki Univ.of Tokyo, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (40167987)
梅田 真郷 東京大学, 薬学部, 助手 (10185069)
工藤 一郎 東京大学, 薬学部, 助教授 (30134612)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥17,500,000 (Direct Cost: ¥17,500,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | Phospholipase A_2 / Prostaglandins / Inflammation / Mast cell / Degranulation / Calcium ion / platelet activating factor / lissencephaly / ホスホリパーゼ / 酸化リン脂質 / セリンエステラーゼ / PAF受容体 / ヒト無脳回症 / WD-40リピート / 脳 / PAF / 酸化脂肪酸 / リポポリサッカライド / TNF / 肝細胞 / 繊維芽細胞 / アラキドン酸 / ロイコトリエン |
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| Research Abstract |
Mammalian cells are known to posseces several type of phospholipase A2. Group II phospholipase A2 was detected in appreciable amounts in rat perioneal mast cells. It was found that the enzyme was is secreted into medium upon stimulation of the cells. The degranulation and eicosanoid production by mast cells are significantly suppressed by the inhibitors of group II phospholipase A2. These observation may suggest that this type of phospholipase A2 play an role in the progression of the degranulation process. A cytosolic phospholipiase A2 with a molecular weight of 85kDa is thought to be a rate limiting enzyme for the production of eicosanoids and leukotrienes. We have discovered that the enzyme has not only phospholipase A2 activity but also lysophospholipase activity. The lysophospholipids produced concomitant with the relase of arachidonaic acid is toxic to the cells because of its detergent-like nature. The cytosolic 85kDa phospholipase A2 may scavenge such lipids by its intrinsic lysophospholipiase activity.
Instead of Ca2+-dependent phospholipase A2 as mentioned above, we have discovered Ca2+-independent phospholipase A2 from mammalian brain. Moreover, we have succeeded in purification and cDNA cloning of the enzyme Unexpectedly, the gene encoding fothe one of the subunit is identical with the causative gene for the Miller-Dieker lissencephaly. This inherited syndrome caused a formation of smooth brain and a death in early age These results suggest that intrascellular phospholipase may play an essental role in the development of central nervous system.
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