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Pharmacological studies on bioactive compounds isolated from marine organisms

从海洋生物中分离的生物活性化合物的药理学研究

基本信息

批准号：
10470479
负责人：
OHIZUMI Yasushi
金额：
$ 6.27万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470479/
关键词：
goniodomin A xestoquinone gramine rerivative maitotoxin amphidinolide B actomyosin ATPase CaィイD12+ィエD1 release nerve growth factor 生理活性物質 9-methyl-7-bromoeudistomin D zooxznthellatoxin B goniodomin A ミオシン筋小胞体アストロサイトーマ細胞骨格筋

项目摘要

Goniodomin A has been shown to cause the conformational change of actin to modify actomyosin ATPase activity. This compound increased and decreased actomyosin ATPase activity, probably through the stimulatory and inhibitory sites on actin, respectively. The troponin/tropomyosin complex binds to actin to inhibit the goniodomin A-induced enhancement of actomyosin ATPase activity, probably by the affecting the stimulatory site on the molecule. Xestoquinone, isolated from a sea sponge Xestospongia sapra, caused a concentration-dependent CaィイD12+ィエD1 release through sulfhydryl modification from skeletal muscle sarcoplasmic rericulum. 5,6-Dibromo-1,2-dimethylgramine evoked CaィイD12+ィエD1 release from skeletal muscle sarcoplasmic reticulum through ryanodine receptors in a concentration-dependent manner. Study of structure-activity relationship for CaィイD12+ィエD1 release indicated that 1-methylation and/or both 5- and 6-bromination are important for CaィイD12+ィエD1 release. Maitotoxin induced a profound increase in CaィイD12+ィエD1 influx in an extracellular CaィイD12+ィエD1-dependent manner. Maitotoxin as well as A-23187 and dubutyryl cyclic AMP caused an acceleration of nerve growth factor (NGF) production in C6-BU-1 cells, as determined by NGF enzyme immunoassay. Maitotoxin activated a voltage-insensitive CaィイD12+ィエD1 channel and accelerated NGF production mediated through a CaィイD12+ィエD1 signaling pathway in C6-BU-1 glioma cells. Amphidinolide B enhanced an interaction of actin and myosin directly and increased CaィイD12+ィエD1 sensitivity of the contractile apparatus mediated through troponin/tropomyosin system, resulting in an increase in the ATPase activity and thus enhanced the contractile response of myofilament.

Goniodomin A 已被证明可引起肌动蛋白构象变化，从而改变肌动球蛋白 ATP 酶活性。该化合物可能分别通过肌动蛋白上的刺激位点和抑制位点增加和降低肌动球蛋白 ATP 酶活性。肌钙蛋白/原肌球蛋白复合物与肌动蛋白结合，可能通过影响分子上的刺激位点来抑制 goniodomin A 诱导的肌动球蛋白 ATP 酶活性增强。 Xestoquinone 是从海海绵 Xestospongia sapra 中分离出来的，通过骨骼肌肌浆网的巯基修饰，引起浓度依赖性的 CaィイD12+ィD1 释放。 5,6-Dibromo-1,2-二甲基禾碱通过兰尼碱受体以浓度依赖性方式诱发骨骼肌肌浆网中的CaィイD12+ィD1释放。 CaィイD12+ィエD1释放的构效关系研究表明，1-甲基化和/或5-和6-溴化对于CaィイD12+ィエD1释放很重要。麦芽毒素以细胞外CaiiD12+ィエD1依赖性方式诱导CaィイD12+ィエD1流入的显着增加。根据 NGF 酶免疫测定结果，麦芽毒素以及 A-23187 和二丁酰环 AMP 导致 C6-BU-1 细胞中神经生长因子 (NGF) 的产生加速。 Maitotoxin 激活电压不敏感的 CaiiD12+ィエD1 通道，并通过 C6-BU-1 神经胶质瘤细胞中的 CaィイD12+ィD1 信号通路介导加速 NGF 的产生。 Amphidinolide B 直接增强肌动蛋白和肌球蛋白的相互作用，并增加肌钙蛋白/原肌球蛋白系统介导的收缩装置的 CaィイD12+ィエD1 敏感性，导致 ATPase 活性增加，从而增强肌丝的收缩反应。