Cell biological control of chronic glomerulonephritis -Analysis of signal transduction molecules in pletelets and glomerular cells-

慢性肾小球肾炎的细胞生物学控制-血小板和肾小球细胞中信号转导分子的分析-

• 批准号: 61570309
• 负责人: FUJIWARA Yoshihiro
• 金额: $ 1.34万
• 依托单位: Osaka University Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570309/
• 关键词: Siqnal transduction mechanism; Phosphoinositide cycle; Inostiol 1,4,5-trisphosphate; Inositol 1,3,4,5-tetrakisphospate; Cultured rat mesangila cell; Angiotensin II; HPLC; イノシトール-1,4,5-トリホスフェイト; アンジオテンシン【II】; ホスホイノシチド・サイクル

Angiotensin II ( AII ) causes the contraction and proliferation of msangial cells, both of which are important in etiology and pathophysiology of chronic glomerulonephritis. Recently lines of evidenc have revealed thath the activation of phosphoinositide cycle ( PI cycle ) is a common signal transduction mechanism in the action of Ca-mobilizing hormones including AII. The possibility has been suggested that the modulation of PI metabolism leads to the discovery of new therapy for chronic glomerulonephritis. Unfortunately, the proeviously published methods for the measurement of inositol phosphates ( IPs ), which should provide direct evidence for activated PI cycle, i.e., phospholipase C-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate, had some disadvantages.In this research project, therefore, we developed the new high performance liquid chromatography ( HPLC ) method, by which we could evaluate AII-induced changes in IPS in cultured rat mesangial cells. The newly develo … More ped HPLC method has enable us to analyze the change in IPs including inositol 1,4,5-trisphosphate ( Ins(1,4,5)P_3 ), inositol 1,3,4-trisphosphate ( Ins(1,3,4)P_3 ), inositol 1,3,4,5-tetrakisphosphate ( Ins(1,3,4,5)P_4 ), inositol pentakisphosphate ( IP_5 ) and inositol hexakisphosphate ( IP_6 ).When the cells were treated with 10-7 M AII, the increase of Ins(1,4,5)P_3 was very rapid and transient. The increase of Ins(1,3,4,5)P_4 was also rapid and remained increased for up to 60 sec. The increase of Ins(1,3,4)P_4 followed their increases. Inositol monophosphate and inositol bisphosphate also increased within 30 sec and 5 sec, respectively. Neither IP_5 nor IP_6 was increased by AII. AII-induced increase of IP_1, IP_2 and inositol trisphosphate showed dose-dependency and were completely inhibited by saralasin, the competitive inhibitor for AII.From these results, we suggest that in cultured rat mesangial cells PI cycle including inositol tris- and tetrakisphosphate pathway is the signal transduction mechanism for AII, which may be coupled with the contraction and proliferation ff the cells. Less

血管紧张素II(AII)引起肾小球系膜细胞的收缩和增殖，在慢性肾小球肾炎的病因学和病理生理学中起重要作用。最近的证据表明，磷脂酰肌醇循环(PI循环)的激活是包括AII在内的钙激活激素作用的一个共同的信号转导机制。提示PI代谢的调节可能为慢性肾小球肾炎的治疗开辟了新的途径。然而，已发表的肌醇磷酸酶(IPs)测定方法存在一定的缺陷，可直接证明磷脂酶C催化的磷脂酰肌醇4，5-二磷酸水解酶激活的PI循环，因此，本研究建立了一种新的高效液相色谱(HPLC)方法，用于评价AII对培养的大鼠肾小球系膜细胞IPS的影响。最新开发的…高效液相色谱(HPLC法)分析了肌醇1，4，5-三磷酸(Ins(1，4，5)P3)、肌醇1，3，4-三磷酸(Ins(1，3，4)P3)、肌醇1，3，4，5-四磷酸(Ins(1，3，4，5)P4)、五磷酸肌醇(IP_5)和六磷酸肌醇(IP_6)等IP_3的变化。INS(1，3，4，5)P4也迅速升高，并持续升高达60s。INS(1，3，4)P4随其升高而升高。一磷酸肌醇和二磷酸肌醇也分别在30秒和5秒内增加。AII对IP_5、IP_6均无明显影响。AII诱导的IP_1、IP_2和肌醇三磷酸的增加呈剂量依赖关系，并可被AII的竞争性抑制剂萨拉拉辛完全抑制。上述结果提示，在培养的大鼠肾小球系膜细胞中，PI周期包括肌醇三和四氢磷酸途径是AII的信号转导机制，这可能与细胞的收缩和增殖有关。较少

项目成果

SungHyo Shin: Biochemical and Biophysical Research Communication. 142. 70-77 (1987)

SungHyo Shin：生物化学和生物物理研究交流。

Yoshimasa Orita Edited by F.Shimizu;I.Kihara;T.Oite: "Cell Proliferation and Glomerulonephritis" Nishimura Co.,Ltd.Niigata, 174 (1986)

折田义政 F.Shimizu、I.Kihara、T.Oite 编：“细胞增殖和肾小球肾炎” Nishimura Co., Ltd. Niigata，174 (1986)

Satoshi Ochi: Biochimica et Biophysica Acta. 927. 100-105 (1987)

Satoshi Ochi：生物化学与生物物理学学报。

Satoshi Ochi: "Phosphoinositide turnover enhanced by angiotensin II in isolated rat glomeluri." Biochimica et Biphysica Acta. 927. 100-105 (1987)

Satoshi Ochi：“在离体大鼠肾小球中，血管紧张素 II 增强了磷酸肌醇的周转。”

申性孝: 日本腎臓学会誌.

Takashi Shin：日本肾脏病学会杂志。