Altus M S, Pearson D, Horiuchi A, Nagamine Y
Biochem J. 1987 Mar 1;242(2):387-92. doi: 10.1042/bj2420387.
The peptide hormone calcitonin induces the accumulation of urokinase-type plasminogen activator (uPA) mRNA in pig kidney LLC-PK1 cells. By itself, inhibition of protein synthesis had a negligible effect on uPA mRNA accumulation. Inhibition of protein synthesis led to two superinductive effects: an increase in calcitonin-induced uPA mRNA accumulation over time, and a shift in the dose-response curve so that lower calcitonin doses became more potent. To explain these two superinductive effects of protein-synthesis inhibition on calcitonin treatment, we demonstrated that the inhibition of protein synthesis increased both calcitonin-induced uPA-gene transcription and uPA-mRNA stability. Different protein-synthesis inhibitors had similar actions, arguing against the possibility that the results were attributable to an anomalous action of a particular inhibitor. The superinductive effects of protein-synthesis inhibition could not be mimicked when a tumour promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), was used instead of calcitonin as an inducer. Calcitonin and TPA exert their effects through different pathways, suggesting a clue to the mechanism of superinduction. Although inhibition of protein synthesis has been reported to increase transcription and mRNA stability in a number of other systems, the one described here appeared unique in combining both effects in the context of hormonal regulation.
肽类激素降钙素可诱导猪肾 LLC-PK1 细胞中尿激酶型纤溶酶原激活剂（uPA）mRNA 的积累。单独而言，蛋白质合成的抑制对 uPA mRNA 的积累影响可忽略不计。蛋白质合成的抑制产生了两种超诱导效应：随着时间推移，降钙素诱导的 uPA mRNA 积累增加，以及剂量反应曲线发生偏移，使得较低剂量的降钙素变得更有效。为了解释蛋白质合成抑制对降钙素处理的这两种超诱导效应，我们证明蛋白质合成的抑制增加了降钙素诱导的 uPA 基因转录和 uPA mRNA 的稳定性。不同的蛋白质合成抑制剂具有相似的作用，这排除了结果归因于特定抑制剂异常作用的可能性。当使用肿瘤促进剂 12-O-十四酰佛波醇 13-乙酸酯（TPA）代替降钙素作为诱导剂时，无法模拟蛋白质合成抑制的超诱导效应。降钙素和 TPA 通过不同途径发挥作用，这为超诱导机制提供了线索。尽管据报道在许多其他系统中蛋白质合成的抑制会增加转录和 mRNA 的稳定性，但此处描述的情况在激素调节背景下将这两种效应结合起来显得独特。
