| Project/Area Number |
13670110
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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 |
General pharmacology
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| Research Institution | NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE |
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Principal Investigator |
INOUE Hiroyasu DEPT. OF PHARMACOLOGY, LABORATORY CHIEF, 薬理部, 室長 (40183743)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | CYCLOOXYGENASE / PROSTAGLANDIN / ENDOTHELIAL CELL / RESVERATROL / PPAR / NUCLEAR RECEPTOR / SHEAR STRESS / GENE EXPRESSION / シクロオキシゲナーゼ |
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| Research Abstract |
Fluid shear stress induces cyclooxygenase (COX) -2 gene expression in vascular endothelial cells. We investigated the underlying mechanism for this induction.
Exposure of human umbilical vein endothelial cells to laminar shear stress in the physiological range (1 to 30 dyne/cm^2) upregulated the expression of COX-2 but not COX-1, a constitutive isozyme of COX. The expression of COX-2 mRNA began to increase within 0.5 hours after the loading of the shear stress and reached a maximal level at 4 hours. Roles of the promoter region and the 3'-untranslated region in the human COX-2 gene were evaluated by the transient transfection of luciferase reporter vectors into bovine arterial endothelial cells. Shear stress elevated luciferase activity via the region between -327 and +59 bp. Mutation analysis indicated that cAMP responsive element (-59/-53 bp) was mainly involved in this response. On the other hand, shear stress selectively stabilized COX-2 mRNA. Moreover, shear stress elevated luciferase activity when a 3'-untranslated region of COX-2 gene containing 17 copies of the AUUUA mRNA instability motif was inserted into the vector.
Transcriptional activation and post-transcriptional mRNA stabilization both contribute to the rapid and sustained expression of COX-2 in response to shear stress.
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