| Project/Area Number |
04454163
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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 |
General medical chemistry
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
TANABE Tadashi National Cardiovascular Center Research Institute, Director, 薬理部, 部長 (60025624)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Shuntaro National Cardiovascular Center Research Institute, Staff, 薬理部, 室員 (50222229)
INOUE Hiroyasu National Cardiovascular Center Research Institute, Senior Staff, 薬理部, 室長 (40183743)
YOKOYAMA Chieko National Cardiovascular Center Research Institute, Director, 薬理部, 室長 (90200914)
宮田 篤郎 国立循環器病センター研究所, 薬理部, 室員 (60183969)
井原 勇人 国立循環器病センター研究所, 薬理部, 室員 (00223298)
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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 |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1993: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1992: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | Fatty Acid / Metabolism / Arachidonic acid / Prostaglandin / Cyclooxygenase / Prostacyclin / Gene / Expression / ジクロオキシゲナーゼ / トロンボキサン / アセチルCoAカルボキシラーゼ |
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| Research Abstract |
To better understand the regulatory mechanisms for the metabolism of fatty acid and its derivatives, we carried out the molecular biological study on the enzymes involved in fatty acid biosynthesis and arachidonic acid metabolism such as acetyl-CoA carboxylase (ACC) , cyclooxygenase (COX) , thromboxane (TX) synthase and prostacyclin (PGI) synthase. In the present project, the following results were obtained. 1.The previously unknown human gene structure for ACC which is the key enzyme for fatty acid biosynthesis, were investigated by cloning and sequence analysis of the cDNA with an open reading frame of about 7 kb. The clones covering the almost entire region for the cDNA were cloned. The 90% of the sequence has been determined and further analysis of the remaining sequence is now in progress. 2.The newly-found COX isozyme COX-2 is recognized as an important enzyme in inflammation process. We determined the entire structure of the human COX-2 gene (8.3 kb) and it is found that the gene (PTGS2) for COX-2 is composed of 10 exons and present on chromosome 1. Further, it was shown with a human monoblastic cell line U937 that a cAMP response element plays an important role in the gene expression of COX-2.3.The gene structure of human TX synthase was determined to consist of 13 exons distributing over a range of 100 kb. An in situ hybridization analysis showed that the TX gene is localized to chromosome 7, and the accumulation of TX synthase mRNA in HEL cells by TPA is ascribed to the stabilization of the mRNA.4.The primary structure of PGI synthase was determined by sequence analyzes of the cloned cDNA and the peptide fragments of the enzyme purified from bovine aortae. The enzyme is composed of 500 amino acids, and the mRNA in cultured endothelial cells was induced by inflammatory cytokines, IL-1, IL-6 and TNF.
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