Schiffmann D, Tas P, Koschel K
Institute of Toxicology, University of Würzburg, Federal Republic of Germany.
Mol Toxicol. 1987;1(4):407-18.
C6 Rat glioma cells acquire an astrocyte-like morphology (cytoplasmic shrinking) after exposure to beta-adrenergic compounds (e.g., isoproterenol) in serum-free medium. This morphological response is mediated by elevation of the intracellular cAMP level and possibly by activation of a kinase phosphorylating and inactivating the myosin-L-kinase in analogy to observations with smooth muscle cells. The result is a disturbance of the stress fiber function, which depends on a cooperation between actin and myosin. Diethylstilbestrol (DES) induces an identical morphological response in these cells under serum-free conditions. However, under the influence of DES no increase of the cAMP level was observed. In addition, at concentrations not inducing these morphological responses, DES inhibits the isoproterenol-induced effect when administered simultaneously or prior to the beta-receptor agonist. DES does not inhibit the isoproterenol-mediated morphological response when added after isoproterenol treatment. Furthermore, if serum is added to cells showing the isoproterenol- or DES-mediated astrocyte-like morphology (DES or isoproterenol present all the time) the cells regain their normal fibroblast-like morphology within 30 min. In view of these results the question arises whether DES interferes with myosin-L-chain phosphorylation or whether it directly interacts with the cytoskeleton stress fiber components, as cytochalasin B1 does. Thus it remains to be established whether the observed effects are related to the estrogenic activity of DES. Similar effects were observed with Syrian hamster embryo fibroblasts under the influence of DES and the naturally occurring steroid estrogen 17-beta-estradiol.
在无血清培养基中，C6大鼠胶质瘤细胞在暴露于β-肾上腺素能化合物（如异丙肾上腺素）后会呈现出星形胶质细胞样形态（细胞质收缩）。这种形态学反应是由细胞内cAMP水平升高介导的，并且可能类似于平滑肌细胞中的观察结果，通过激活一种激酶使肌球蛋白轻链激酶磷酸化并使其失活来实现。结果是应力纤维功能受到干扰，而应力纤维功能依赖于肌动蛋白和肌球蛋白之间的协同作用。己烯雌酚（DES）在无血清条件下可在这些细胞中诱导相同的形态学反应。然而，在DES的影响下，未观察到cAMP水平升高。此外，在不诱导这些形态学反应的浓度下，DES在与β受体激动剂同时给药或先于其给药时会抑制异丙肾上腺素诱导的效应。在异丙肾上腺素处理后添加DES时，它不会抑制异丙肾上腺素介导的形态学反应。此外，如果向呈现异丙肾上腺素或DES介导的星形胶质细胞样形态的细胞（始终存在DES或异丙肾上腺素）中添加血清，细胞会在30分钟内恢复其正常的成纤维细胞样形态。鉴于这些结果，问题就出现了，DES是干扰了肌球蛋白轻链的磷酸化，还是像细胞松弛素B1一样直接与细胞骨架应力纤维成分相互作用。因此，仍有待确定观察到的效应是否与DES的雌激素活性有关。在DES和天然存在的甾体雌激素17-β-雌二醇的影响下，叙利亚仓鼠胚胎成纤维细胞也观察到了类似的效应。
