Theonezolide A, a novel marine macrolide, induces drastic shape change in rabbit platelets by reorganization of microtubules

Theonezolide A, a novel marine macrolide, induces drastic shape change in rabbit platelets by reorganization of microtubules
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DOI:
10.1016/s0049-3848(02)00355-9
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发表时间:
2002-11-01
影响因子:
7.5
通讯作者:
Nakahata, N
Nakahata, N
中科院分区:
医学3区
文献类型:
--
作者:
Mitsui-Saito, M;Ohkubo, S;Nakahata, N

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Theonezolide A,一种海洋大环内酯,和凝血酶引起形状改变,随后在兔血小板中聚集。通过光透射减少来估计,Theonezolide a诱导的血小板形状变化比凝血素诱导的血小板形状变化更大。电镜形态学研究表明,theonezolide A改变了血小板的形状,出现了不同数量的长伪足,失去了其盘状的形状。teonezolide a诱导的形状变化被微管稳定剂紫杉醇(taxol)抑制,而不被肌动蛋白解聚剂细胞松弛素B (cytochalasin B)抑制。相反,凝血酶诱导的形状变化被细胞松弛素B (cytochalasin B)抑制,而紫杉醇(taxol)没有。共聚焦荧光显微镜显示,经theonezolide A处理的血小板中,周向微管束消失。theonezolide A对牛脑分离的微管聚合无直接影响,表明其间接引起微管重组。这些结果表明,theonezolide A通过重组兔血小板微管引起剧烈的形状改变。因此,theonezolide A是一种检测细胞微管重组的有用药物。(C) 2002 Elsevier Science Ltd.版权所有。
Theonezolide A, a marine macrolide, and thrombin caused a shape change followed by an aggregation in the rabbit platelets. Theonezolide A-induced platelet shape change, estimated by a decrease in light transmission, appeared to a greater extent than thrombin-induced one. Morphological studies using an electron microscope showed that theonezolide A changed platelet shape with various numbers of long pseudopods, loosing their discoid shape. Theonezolide A-induced shape change was inhibited by a microtubule-stabilizing agent, taxol, but not by an actin-depolymerizing agent, cytochalasin B. In contrast, thrombin-induced shape change was inhibited by cytochalasin B but not by taxol. Confocal fluorescence microscopy showed that circumferential microtubule bundle disappeared in the platelets treated with theonezolide A. Theonezolide A had no direct effect on polymerization of microtubules isolated from bovine brain, indicating that it indirectly causes microtubule reorganization. These results suggest that theonezolide A induces drastic shape change through reorganization of microtubules in rabbit platelets. Thus, theonezolide A is a useful drug to examine microtubule reorganization in the cells. (C) 2002 Elsevier Science Ltd. All rights reserved.