THE EFFECTS OF TAXOL ON CYTOSKELETAL COMPONENTS IN CULTURED FIBROBLASTS AND EPITHELIAL-CELLS

THE EFFECTS OF TAXOL ON CYTOSKELETAL COMPONENTS IN CULTURED FIBROBLASTS AND EPITHELIAL-CELLS
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DOI:
10.1002/cm.970030402
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发表时间:
1983-01-01
影响因子:
--
通讯作者:
GOLDMAN, RD
GOLDMAN, RD
中科院分区:
其他
文献类型:
--
作者:
GREEN, KJ;GOLDMAN, RD

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紫杉醇促进微管(MT)组装在体外,并诱导细胞骨架重组成不寻常的MT阵列在培养细胞。研究了紫杉醇对中间纤维也有间接影响的可能性。在用1-10 μ M紫杉醇处理1-24小时的幼仓鼠肾(BHK-21)和人皮肤(ENSON)成纤维细胞中,该药物诱导的变化与秋水仙碱产生的变化相似。这些包括主要细胞延伸的损失,细胞器重新分配到核周位置和运动抑制。跳跃粒子运动不受抑制。皱褶和丝状足形成继续,表明细胞可存活长达24 h。用紫杉醇处理的活的成纤维细胞的偏振光显微镜显示核周双折射材料的存在,其通过免疫荧光检查。在对照细胞中,IF和MT从胞核区域放射并延伸至细胞周边。在紫杉醇处理的细胞中,MT和IF被排除在细胞边缘之外,形成大的中央束。在上皮细胞系PtK 2和PAM中,IF的角蛋白系统不会重新分布;在PtK 2中,IF的第二成纤维细胞样系统在紫杉醇治疗期间重新分布到核周位置。超微结构分析表明,紫杉醇处理的成纤维细胞含有平行阵列的交叉桥MT-IF和MT束不包括IF。上皮细胞含有占主导地位的IF-自由MT束,其被组织成六边形包装阵列。在这些束中,MT经常表现出钩或其他不完整的MT配置文件,并通过丝状物质连接。
Taxol promotes microtubule (MT) assembly in vitro and induces the reorganization of the cytoskeleton into unusual MT arrays in cultured cells. The possibility that taxol also has an indirect effect on intermediate filaments (IF) was investigated. In baby hamster kidney (BHK-21) and human skin (ENSON) fibroblasts treated with 1-10 .mu.M taxol for 1-24 h, the drug induces changes which are similar to those produced by colchicine. These include a loss of major cellular extensions, a redistribution of organelles to a perinuclear location and an inhibition of locomotion. Saltatory particle movements are not inhibited. Ruffling and filopod formation continue, indicating that cells are viable up to 24 h. Polarized light microscopy of living fibroblasts treated with taxol reveals the presence of perinuclear birefringent material which was examined by immunofluorescence. In control cells, IF and MT radiate from a juxtanuclear region and extend to the cell periphery. In taxol-treated cells, MT and IF are excluded from cell margins, forming large central bundles. In the epithelial cell lines PtK2 and PAM, the keratin system of IF does not become redistributed; in PtK2, a 2nd fibroblastlike system of IF does become redistributed to a perinuclear position during taxol treatment. Ultrastructural analyses show that taxol-treated fibroblasts contain parallel arrays of cross-bridged MT-IF and bundles of MT exclusive of IF. Epithelial cells contain a predominance of IF-free MT bundles which are organized into hexagonally packed arrays. In these bundles, MT frequently exhibit hooks or other incomplete MT profiles and are linked by filamentous material.