The new anti-actin agent dihydrohalichondramide reveals fenestrae-forming centers in hepatic endothelial cells
The new anti-actin agent dihydrohalichondramide reveals fenestrae-forming centers in hepatic endothelial cells
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DOI：
10.1186/1471-2121-3-7
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发表时间：
2002-03-21
期刊：
影响因子：
--
通讯作者：
Wisse, E
中科院分区：
文献类型：
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作者：
Braet, F;Spector, I;Wisse, E
背景：肝窦内皮细胞（LSECs）对不同的抗肌动蛋白药物的反应是通过增加它们的心房数目来实现的。当使用米沙金内酯处理LSECs时，可以观察到与窗形成有关的新结构。在这项研究中，我们研究了两种新的肌动蛋白结合剂对窗动力学的影响。高分辨率显微镜，包括免疫细胞化学和荧光和扫描电子显微镜的组合应用。结果：Halichondramide和二氢Halichondramide在10分钟内破坏微丝，30分钟内使窗数增加一倍。双氢halichondramide诱导成窗中心，而halichondramide只显示成窗中心，而没有随直径增加而附着的成排的成窗。相关显微镜显示筛板和孔形成中心没有肌动蛋白丝（f -肌动蛋白）。脐静脉内皮细胞和骨髓窦内皮细胞的对比实验显示，细胞收缩，但没有出现窗或窗形成中心。结论：(1)对迄今为止测试的所有抗肌动蛋白药物进行比较，发现misakinolide和dihydrohalichondramide唯一的共同之处是它们的钩端封盖活性；（II）这种活动似乎减缓了窗的形成过程，以至于有可能解决窗的形成中心；（III）由于微丝断裂而形成的窗可能是LSECs所特有的。
Background: Liver sinusoidal endothelial cells (LSECs) react to different anti-actin agents by increasing their number of fenestrae. A new structure related to fenestrae formation could be observed when LSECs were treated with misakinolide. In this study, we investigated the effects of two new actin-binding agents on fenestrae dynamics. High-resolution microscopy, including immunocytochemistry and a combination of fluorescence- and scanning electron microscopy was applied.Results: Halichondramide and dihydrohalichondramide disrupt microfilaments within 10 minutes and double the number of fenestrae in 30 minutes. Dihydrohalichondramide induces fenestrae-forming centers, whereas halichondramide only revealed fenestrae-forming centers without attached rows of fenestrae with increasing diameter. Correlative microscopy showed the absence of actin filaments (F-actin) in sieve plates and fenestrae-forming centers. Comparable experiments on umbilical vein endothelial cells and bone marrow sinusoidal endothelial cells revealed cell contraction without the appearance of fenestrae or fenestrae-forming centers.Conclusion: (I) A comparison of all anti-actin agents tested so far, revealed that the only activity that misakinolide and dihydrohalichondramide have in common is their barbed end capping activity; (II) this activity seems to slow down the process of fenestrae formation to such extent that it becomes possible to resolve fenestrae-forming centers; (III) fenestrae formation resulting from microfilament disruption is probably unique to LSECs.