Analysis of syndecan-4 core protein as a receptor for antithrombin III

Syndecan-4 核心蛋白作为抗凝血酶 III 受体的分析

• 批准号: 18390479
• 负责人: MINAMIYA Yoshihiro
• 金额: $ 11.19万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390479/
• 关键词: Acute Respirator Distress Syndrome; antithrombin III; syndecan-4

Recently, the outcome of the treatment for Acute Respiratory Distress Syndrome (ARDS) has been improved. However, the prognosis of ARDS is still poor. Especially, the prognosis of ARDS associated with sepsis is extremely poor. Therefore, we should establish the method to cure ARDS as soon as possible. Antithrombin III (AT) sometimes applies for the treatment of disseminated intravascular coagulation, because of its anti-coagulant effect. AT binds and inactivates thrombin and other coagulants. On the other hand, the meta-analysis demonstrated that the effectiveness of AT for severe sepsis. This results suggests that AT has an anti-inflammatory effect. We demonstrated that AT most likely reduces F-actin formation in neutrophil thereby reducing neutrophil accumulation in the lung, which would in turn inhibit oxygen radical production in the rat lung. We also demonstrated that pretreatment of neutrophil with both AT and latent-AT attenuate F-actin formation and decreasing of deformability … More due to fMLP treatment. These data suggest that there must be new receptor for AT on the cell membrane of neutrophil. In 2006, at first we examined expression of syndecan-4 and removed heparan sulfate from isolated human neutrophil. However, for these kinds of experiment, we need a large amount of neutrophil. In 2007, we found that human tumor cell line HTI080 express syndecan-4. Therefore, we used HT1080 instead of isolated human neutrophil. After removing heparan sulfate from cell surface of the cultured tumor cell line HT1080 using heparinase or sodium chlorate, AT was still bound to AT except for heparin binding site. Then, we isolated and analyzed the proteins bound to AT using mass spectrometry. Syndecan-4, one of the glycosaminoglycan, was detected even when heparin sulfate was removed from the cell surface using heparinase or sodium chlorate. To further proof the results, we applied IP-western and demonstrated that AT bound to syndecan-4 even after removing heparin sulfate using heparinase or sodium chlorate. These data suggest syndecan-4 is a receptor for AT. Less

最近，与败血症相关的ARDS的预后是尽快治愈ARDS的预后。荟萃分析表明，严重败血症的效率是抗炎作用。用毒性和潜在的F-Actingormabi lity毒的中性粒细胞，因为FMLP治疗更多。硫酸盐中的中性粒细胞，我们需要大量的中性粒子，我们发现人类肿瘤细胞系HTI080 Express Syndecan-4我们使用了HT1080。然后，使用肝素酶或氯酸钠的ht1080在肝素结合位点的例外。肝素酶或钠氯酸盐