Basic study for development of a novel therapeutic strategy, targeting the extracellular ATP hydrolyzing enzyme, CD39 to protect from vascular endothelial disorder.
| Project/Area Number |
20590088
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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 |
Biological pharmacy
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| Research Institution | Takasaki University of Health and Welfare |
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Principal Investigator |
MATSUOKA Isao Takasaki University of Health and Welfare, 薬学部, 教授 (10145633)
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| Co-Investigator(Kenkyū-buntansha) |
YOMOGIDA Sinnichi 高崎健康福祉大学, 薬学部, 准教授 (90250802)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 心血管 / 炎症 / 病態生理 / 細胞内情報伝達 / 血管内皮細胞 / 細胞外ヌクレオチド代謝 / CD39 / 遺伝子発現 / HMG-CoA還元酵素阻害剤 / PI3-キナーゼ / Akt / HIF-1α / P2受容体 / 炎症性サイトカイン / プロモーター解析 |
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| Research Abstract |
Vascular endothelial cells express highly active ecto-nucleoside diphosphohydrolase 1 (CD39) that hydrolyzes extracellular ATP and ADP into AMP. CD39 plays a critical role in the regulation of vascular homeostasis. In this study, we found that various inflammatory cytokines including IL-1β, TNF-α and IFN-γ, impaired the ATP hydrolysis and CD39 mRNA expression, whereas HMG-CoA reductase inhibitor (statin) caused time- and concentration-dependent increase in ATP and ADP hydrolysis accompanied by an up-regulation of CD39 mRNA expression. Statin-induced up-regulation of CD39 mRNA expression was involved in an inhibition of small G protein Rho function. These results suggest that the inhibition of Rho-dependent signaling is a promising strategy to increases vascular CD39 expression.
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Report
(4 results)
Research Products
(33 results)
