Development of drug by use of protease cascade of prostasin

利用前列腺素的蛋白酶级联开发药物

• 批准号: 18390252
• 负责人: TOMITA Kimio
• 金额: $ 11.51万
• 依托单位: Kumamoto 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-18390252/
• 关键词: hypertension; Na; prostasin; serine protease; protease cacade; プロテアーゼ; 腎; 上皮型Naチャネル; アルドステロン

Hypertension is one of the strong factors to damage vascular system. Sodium regulation in the kidney is one of the most important factors for the regulation of blood pressure. Epithelial sodium channel is key protein in the regulation of Na balance. We reported that a new serine protease prostasin can activate epithelial sodium channel in cultured cells. Prostasin was stimulated by aldosterone in vitro and in vivo experiments. In human, urinary prostasin excretion was elevated in primary aldosteronism, suggesting that prostasin may have significant roles in the regulation of blood pressure. Therefore, we have investigated to elucidate the roles of prostasin in the regulation of blood pressure by use of proteomics. At first, we have isolated several proteins which activate serine protease prostasin. We have already isolated three clones which activated prostasin activity. We now under experiments to purify and identify of amino acid of these proteinsThis projects is now underway. We must continue further experiments.

高血压是损害血管系统的强大因素之一。肾脏中的钠调节是调节血压的最重要因素之一。上皮钠通道是调节Na平衡的关键蛋白。我们报告说，一种新的丝氨酸蛋白酶前列腺素可以激活培养细胞中的上皮钠通道。醛固酮在体外和体内实验中刺激前列腺素。在人类中，原发性醛固酮基因的尿中前列腺素排泄升高，表明前列腺素可能在血压调节中具有重要作用。因此，我们研究了通过使用蛋白质组学来阐明前列腺素在调节血压中的作用。最初，我们分离了几种激活丝氨酸蛋白酶前列腺素的蛋白质。我们已经分离了三个激活前列腺素活性的克隆。现在，我们正在进行实验，以净化和识别这些蛋白质项目的氨基酸现在正在进行中。我们必须继续进一步实验。

项目成果

Successful treatment of a patient with severe calcific uremic arteriolopathy(calciphylaxis) by etidronate disodium

依替膦酸二钠成功治疗严重钙化性尿毒症性小动脉病（钙化防御）患者

• 发表时间: 2006
• 期刊: Am J Kidney Dis. 48(1)
• 作者: Shiraishi;N
• 通讯作者: N

Down-regulation of V2 vasopressin receptor in dehydration : mechanisms and the role of renal prostaglandin synthesis.

脱水中 V2 加压素受体的下调：机制和肾前列腺素合成的作用。

• 发表时间: 2007
• 期刊: Am.J.Physiol.Renal Physiol. (印刷中)
• 作者: Machida K;et al.
• 通讯作者: et al.

Successful treatment of a patient with severe calcific arteriolopathy(alciohylaxis)by etidronate disodium

依替膦酸二钠成功治疗严重钙化性小动脉病（抗酒精）患者

• 发表时间: 2006
• 期刊: Am J Kidney Dis. 48(1)
• 作者: Shiraishi N;ら
• 通讯作者: ら

Target haemoglobin concentrations in chronic kidney disease

慢性肾脏病的目标血红蛋白浓度

• 发表时间: 2007
• 期刊: Lancet 369
• 作者: Nonoguchi;H.;Nakayama;Y.;Tomita;K. et.al.
• 通讯作者: K. et.al.

Inhibition of prostasin-induced ENaC activities by PN-1 and regulation of PN-1 expression by TGF-betal and aldosterone

PN-1 抑制前列腺素诱导的 ENaC 活性以及 TGF-β 和醛固酮调节 PN-1 的表达

• 发表时间: 2006
• 期刊: Kidoney Int. 70(8)
• 作者: Wakida N;ら
• 通讯作者: ら