Seifert S C, Gelehrter T D
Proc Natl Acad Sci U S A. 1978 Dec;75(12):6130-3. doi: 10.1073/pnas.75.12.6130.
Glucocorticoids rapidly and completely inhibit intracellular plasminogen activator activity in rat hepatoma cells, as assayed by the solubilization of 125I-labeled fibrin. Experiments in which extracts of dexamethasone-treated cells are mixed with extracts of control cells demonstrate an inhibitor of protease activity. Plasminogen activator is found primarily in the particulate fraction of cell lysates, whereas the inhibitor is localized in the soluble fraction. Variant cells have been isolated previously that are fully resistant to the dexamethoasone inhibition of plasminogen activator activity. These variants have no demonstrable inhibitor activity, whereas plasminogen activator in these cells is fully sensitive to inhibitor from wild-type cells. Thus, the basis for hormone resistance appears to be the failure of dexamethasone to induce an inhibitor.
通过对125I标记的纤维蛋白进行溶解测定发现，糖皮质激素能迅速且完全抑制大鼠肝癌细胞内纤溶酶原激活剂的活性。将地塞米松处理过的细胞提取物与对照细胞提取物混合进行实验，结果显示存在一种蛋白酶活性抑制剂。纤溶酶原激活剂主要存在于细胞裂解物的颗粒部分，而抑制剂则定位于可溶性部分。先前已分离出对糖皮质激素抑制纤溶酶原激活剂活性完全耐药的变异细胞。这些变异细胞没有可检测到的抑制剂活性，而这些细胞中的纤溶酶原激活剂对野生型细胞的抑制剂完全敏感。因此，激素耐药的基础似乎是地塞米松未能诱导出抑制剂。
