Pathophysiological role of lipid molecules produced by 12/l5-lipoxygenase
| Project/Area Number |
12470024
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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 | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Kanazawa University |
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Principal Investigator |
YOSHIMOTO Tanihiro Kanazawa University, Pharmacology, Professor, 大学院・医学系研究科, 教授 (60127876)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Yashitaka Kanazawa University, Pharmacology, Instructor, 大学院・医学系研究科, 助手 (10236333)
HIGUCHI Yoshihiro Kanazawa University, Pharmacology, Instructor, 大学院・医学系研究科, 助手 (10019630)
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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 |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | Lipoxygenase / Macrophage / Oxidized LDL / LDL receptor-related protein / Cholesterol ester / Translocation / 12 / 15-リポキシゲナーゼ / 受容体 / スカベンジャー受容体 |
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| Research Abstract |
Lipoxygenase incorporates a molecular oxygen regiospecifically and stereospeciflcally into unsaturated fatty acids. There are four classes of enzymes in mammalian tissues; 5-, 8-, 12-, and 15-lipoxygenases, named by the number indicating oxygenation site of arachidonic acid as a substrate. Among the enzymes, 12-lipoxygenases are widely distributed in various tissues and species, and there are three isoforms: platelet, leukocyte and epidermis types. Since the leukocyte 12-lipoxygenase and 15-lipoxygenase-1 are highly related in their primary structures and enzymological properties, these enzymes are collectively called as 12/15-lipoxygenase. A number of evidences support the role of 12/15-lipoxygenase in LDL oxidation. In order to investigate precise mechanisms of the 12/15-lipoxygenase-mediated LDL oxidation, we established a mouse macrophage-like J774A1 cell line overexpressing porcine leukocyte 12-lipoxygenase. The presence of regio- and stereospeciflcally oxygenated product of cholesteryl linoleate in the LDL indicates that the 12/15-lipoxygenase is responsible for cell-mediated LDL oxidation. We also showed that LDL receptor-related protein (LRP) was required for the enzyme-mediated LDL oxidation by macrophages. Furthermore, cholesterol ester selectively transferred from the LDL particle to the plasma membrane via LRP is oxygenated by 12/15-lipoxygenase translocated to this membrane:
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Report
(4 results)
Research Products
(21 results)
