Basic study for development of a novel therapeutic strategy, targeting the extracellular ATP hydrolyzing enzyme, CD39 to protect from vascular endothelial disorder.

开发新型治疗策略的基础研究，以细胞外 ATP 水解酶 CD39 为靶点，以预防血管内皮疾病。

• 批准号: 20590088
• 负责人: MATSUOKA Isao
• 金额: $ 2.91万
• 依托单位: Takasaki University of Health and Welfare
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590088/
• 关键词: 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

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.

血管内皮细胞表达高活性的胞外核苷二磷酸水解酶1（CD 39），其将胞外ATP和ADP水解成AMP。CD 39在调节血管稳态方面发挥着关键作用。在本研究中，我们发现多种炎性细胞因子包括IL-1β、TNF-α和IFN-γ，损害ATP水解和CD 39 mRNA表达，而HMG-CoA还原酶抑制剂（他汀类）引起ATP和ADP水解的时间和浓度依赖性增加，同时上调CD 39 mRNA表达。他汀诱导的CD 39 mRNA表达的上调参与了小G蛋白Rho功能的抑制。这些结果表明，抑制Rho依赖性信号传导是增加血管CD 39表达的有希望的策略。

项目成果

ATP受容体を介する細胞応答における細胞外ATP分解酵素Nucleotide triphosphate diphosphohydrolase 1の役割

细胞外 ATP 酶核苷酸三磷酸二磷酸水解酶 1 在 ATP 受体介导的细胞反应中的作用

• 发表时间: 2008
• 作者: 松岡功;伊藤政明;蓬田伸一
• 通讯作者: 蓬田伸一

Regulation of purinergic signaling by prostaglandin E2 in murine macrophages

• DOI: 10.1254/jphs.08087fp
• 发表时间: 2008-08-01
• 期刊: JOURNAL OF PHARMACOLOGICAL SCIENCES
• 影响因子: 3.5
• 作者: Ito, Masaaki;Matsuoka, Isao
• 通讯作者: Matsuoka, Isao

Mechanism and Role of High Density Lipoprotein-induced Activation of AMP-activated Protein Kinase in Endothelial Cells

• DOI: 10.1074/jbc.m109.043869
• 发表时间: 2010-02-12
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Kimura, Takao;Tomura, Hideaki;Okajima, Fumikazu
• 通讯作者: Okajima, Fumikazu

Effects of prostaglandin E_2 on UDP-induced Ca^<2+> signaling in human P2Y_6 receptor expressed 1321N1 cells

前列腺素E_2对表达人P2Y_6受体的1321N1细胞中UDP诱导的Ca^2信号传导的影响

• 发表时间: 2010
• 作者: Ito M;Matsuoka I
• 通讯作者: Matsuoka I

Effects of HMG-CoA reductase inhibitors on vascular endothelial ecto-nucleotidase activities

HMG-CoA还原酶抑制剂对血管内皮核酸外切酶活性的影响

• 发表时间: 2010
• 作者: Matsuoka I;Ito M;Yomogida S
• 通讯作者: Yomogida S