Ryan M P, Higgins P J
Laboratory of Cell and Molecular Biology, Veterans Administration Medical Center, Albany, New York 12208.
J Cell Physiol. 1988 Oct;137(1):25-34. doi: 10.1002/jcp.1041370104.
Murine sarcoma virus-transformed rat fibroblasts (KNRK cells) undergo marked cytoarchitectural reorganization during in vitro exposure to sodium-n-butyrate (NaB) resulting in restoration of (1) a more typical fibroblastoid morphology, (2) proper cell-to-cell orientation, and (3) substratum adherence. Augmented cell spreading, involving greater than 90% of the population, was a function of culture density and time of exposure to NaB (2 mM final concentration). Induced cell spreading reflected a 2.5- to 3.0-fold increase in both total cellular actin content and deposition of actin into the detergent-resistant cytoskeleton. Cytoskeletal actin deposition in response to NaB was accompanied by the formation of occasionally dense, parallel alignments of F-actin-containing microfilaments and by a dramatic increase in the size and incidence of actin-enriched membrane ruffles. Long-term NaB-treated cells exhibited parallel orientations of microfilaments similar to those found in untransformed fibroblasts. Increased cytoskeletal actin occurred within 24 hr of NaB exposure, correlating with the initial reorganization of actin-containing microfilaments detected microscopically, and reflected concomitant 3-fold increases in cellular alpha-actinin and fibronectin content. In contrast, the amount of vimentin, tropomyosin, and tubulin in NaB-treated cells was significantly decreased. NaB-induced morphologic restructuring of sarcoma virus-transformed fibroblasts, thus, impacts on all three basic cytoskeletal systems. Selective increases, however, were evident in particular cytoskeletal proteins (actin, alpha-actinin, fibronectin) implicated in microfilament networking and cell spreading.
鼠肉瘤病毒转化的大鼠成纤维细胞（KNRK细胞）在体外暴露于正丁酸钠（NaB）期间会经历显著的细胞结构重组，从而导致以下情况恢复：（1）更典型的成纤维细胞样形态；（2）正确的细胞间定向；（3）与基质的黏附。细胞铺展增加，涉及超过90%的细胞群体，这是培养密度和暴露于NaB（终浓度2 mM）时间的函数。诱导的细胞铺展反映出总细胞肌动蛋白含量以及肌动蛋白沉积到抗去污剂细胞骨架中的量增加了2.5至3.0倍。响应NaB的细胞骨架肌动蛋白沉积伴随着偶尔密集、平行排列的含F-肌动蛋白微丝的形成，以及富含肌动蛋白的膜皱褶的大小和发生率的显著增加。长期用NaB处理的细胞表现出与未转化的成纤维细胞中相似的微丝平行定向。细胞骨架肌动蛋白的增加在暴露于NaB的24小时内出现，与显微镜下检测到的含肌动蛋白微丝的初始重组相关，并反映出细胞α-辅肌动蛋白和纤连蛋白含量同时增加了3倍。相比之下，用NaB处理的细胞中波形蛋白、原肌球蛋白和微管蛋白的量显著减少。因此，NaB诱导的肉瘤病毒转化的成纤维细胞的形态重组影响所有三个基本的细胞骨架系统。然而，在与微丝网络和细胞铺展相关的特定细胞骨架蛋白（肌动蛋白、α-辅肌动蛋白、纤连蛋白）中明显出现了选择性增加。
