| Project/Area Number |
12671598
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Osaka University |
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Principal Investigator |
TASAKA Keiichi (2001) Osaka University, Graduate School of Medicine, Associate professor, 医学系研究科, 助教授 (50155058)
山本 敏也 (2000) 大阪大学, 医学系研究科, 助手 (80283787)
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| Co-Investigator(Kenkyū-buntansha) |
MORISHIGE Ken-ichiro Osaka University, Graduate School of Medicine, Assistant professor, 医学系研究科, 助手 (90283788)
OHMICHI Masahide Osaka University, Graduate School of Medicine, Assistant professor, 医学系研究科, 助手 (10283764)
SAKATA Masahiro Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (10260639)
田坂 慶一 大阪大学, 医学系研究科, 助教授 (50155058)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Estrogen / lipoprotein lipase / ER-α / matrix metalloproteinase / マトリツクスメタロプロテイネース / マトリックスメタロプロテイネー / 肥満 / 動脈硬化 / LPL |
|---|
| Research Abstract |
Many reports described that estrogen replacement therapy is effective for preventing postmenopausal women against hyperlipidemia and atherosclerosis. We studied the mechanism underlying this estrogen-dependent lipid metabolism by lipoprotein lipase (LPL) gene promoter analyzes using mouse 3T3-L1 cells. We identified a novel (not consensus) estrogen responsive element, which is located -1856/-1850 of LPL promoter lesion by employing a set of 5 -deletion mutants of LPL-CAT reporter. We also confirmed that this repressive effect of estrogen is mainly mediated by estrogen receptor (ER)-α by co-transfection experiments, whereas ER-β, another estrogen receptor, showed only marginal effect. Next, we investigated effects of estrogen on matrix metalloproteinase activity that has an important role for forming atherosclerotic plaque using human umbilical vein endothelial cells. Zymography demonstrated that six-hour treatment of estrogen inhibited MMP2 activity in a dose-dependent manner. These results suggest that estrogen inhibits hyperlipidemia and atherosclerosis by various mechanisms.
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