Actin depolymerize agents isolated from marine organism

从海洋生物中分离出肌动蛋白解聚剂

• 批准号: 11556057
• 负责人: KARAKI Hideaki
• 金额: $ 8.7万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11556057/
• 关键词: actin; depolimerization; biology; pectenotoxin 2; mycalolide B, and; swinholide A; bisteonellide A

Pectenotoxin-2 (PCTX-2), which is one of the causation of the Diarrhetic Shellfish Poisoning (DSP), is a family of cyclic polyether macrolide toxin isolated from scallop Patinopecten yessoensis. Although PCTX-2 has a potent cytotoxic activities against several cancer cell lines, the biochemical activity of PCTX-2 has not been determined yet. To clarify the biochemical activity of PCTX-2 is the aime in this study. PCTX-2 inhibited the contractions elicited by 72.7 mM KCl or 1 mM phenyrephrine in a concentration dependent manner in the isolated rat aorta. In A10 cells, actin stressfiber in the central portion but not in the periphery of the cell was disrupted by PCTX-2 without any visible change in the cell shape. By monitoring fluorescent intensity of pyrenyl-actin, PCTX-2 was found to inhibit the velocity and the degree of actin polymerization in a concentration dependent manner. In addition, PCTX-2 decreased viscosity of F-actin measured with the falling ball viscometry. Stoichiometric analysis indicated that PCTX-2 forms 1 : 4 complex with G-actin. These results suggest that PCTX-2 is a potent natural actin depolymerizing compound with unique mode of action.We also examined the other marine metabolites, such as mycalolide B, swinholide A and bisteonellide A, and revealed their unique biological activities. In addition, we applied these agents on actin biology.

贝毒素-2(PCTX-2)是从对虾夷扇贝中分离到的一类环状聚醚大环内酯类毒素，是引起贝类腹泻性中毒的原因之一。尽管PCTX-2对几种癌细胞具有很强的细胞毒活性，但其生化活性尚未确定。阐明PCTX-2的生化活性是本研究的目的。PCTX-2对72.7 mM氯化钾或1 mM去甲肾上腺素引起的大鼠离体主动脉收缩具有浓度依赖性抑制作用。在A10细胞中，细胞中央部分的肌动蛋白应激纤维被PCTX-2破坏，但细胞形态没有明显变化。通过监测肌动蛋白的荧光强度，发现PCTX-2以浓度依赖的方式抑制肌动蛋白的聚合速度和程度。此外，通过落球粘度计测定，PCTX-2还降低了F-肌动蛋白的粘度。化学计量分析表明，PCTX-2与G-肌动蛋白形成1：4的络合物。这些结果表明，PCTX-2是一种有效的天然肌动蛋白解聚化合物，具有独特的作用方式。我们还检测了其他海洋代谢物，如霉菌内酯B、Swinholide A和双十八内酯A，并揭示了它们独特的生物活性。此外，我们还将这些试剂应用于肌动蛋白生物学。

项目成果

H.Katayama,M.Hori,K.Sato, ら: "Role of actin fiber formation in host cells for the multiplication of canine distemper virus."Jpn.J.Pharmacol.. (In press). (2000)

H.Katayama、M.Hori、K.Sato 等人：“宿主细胞中肌动蛋白纤维形成对犬瘟热病毒增殖的作用”。Jpn.J.Pharmacol.（出版中）。

H.Katayama,M.Hori K.Sato, ら: "Role of actin fiber formation in host cells for the multiplication of canine distemper virus."Jpn.J.Pharmacol.. In press. In press (2000)

H.Katayama、M.Hori K.Sato 等人：“宿主细胞中肌动蛋白纤维形成对犬瘟热病毒增殖的作用”。Jpn.J.Pharmacol. 出版中（2000 年）。

K.Takahashi ら: "Regulation of shortenning velocity by calponin in intact contracting smooth muscles"Biochem.Biophys.Res.Comm.. 279. 150-157 (2000)

K. Takahashi 等：“完整收缩平滑肌中钙调蛋白对缩短速度的调节”Biochem.Biophys.Res.Comm.. 279. 150-157 (2000)

H.Takahashi, R.Yoshimoto, K.Fuchibe, A.Fujishige, M.Mitsui-Saito, M.Hori, H.Ozaki, H.Yamamura, N.Awata, S.Taniguchi, M.Katsuki, T.Tsuchiya and H.Karaki: "Regulation of shortenning velocity by calponin in intact contracting smooth muscles."Biochem.Biophys.

H.Takahashi、R.Yoshimoto、K.Fuchibe、A.Fujishige、M.Mitsui-Saito、M.Hori、H.Ozaki、H.Yamamura、N.Awata、S.Taniguchi、M.Katsuki、T.Tsuchiya 和

掘正敏、松浦康浩、尾崎博ら: "海洋由来天然生理活性物質、ペクテノトキシン-2のアクチン重合阻害作用"日本薬理学雑誌. 114. 225-229 (1999)

Toshi Hori、Yasuhiro Matsuura、Hiroshi Ozaki 等：“来自海洋的天然生理活性物质果胶毒素-2 的肌动蛋白聚合的抑制作用”日本药理学杂志 114. 225-229 (1999)。