Karin M, Herschman H R
Eur J Biochem. 1981 Jan;113(2):267-72. doi: 10.1111/j.1432-1033.1981.tb05062.x.
Metallothioneins are induced by both Zn2+ and dexamethasone in HeLa cells grown in serum-free medium. Dexamethasone is able to induce metallothionein synthesis in HeLa cells in virtually zinc-free medium ([Zn2+] = .01 microM). The presence of dexamethasone does not shift the dose/response curve for metallothionein induction by Zn2+, further indicating that the two inducers work through independent mechanisms. Dexamethasone stimulates Zn2+ uptake 1.7-fold over 24 h. However, there is no increase in Zn2+ uptake during the first 4 h. In contrast, metallothionein synthesis in response to either Zn2+ or dexamethasone is clearly observable within 4 h of exposure to either inducer. The increased intracellular 65Zn2+ content observed at 24 h is completely accounted for by the increased level of metal bound to metallothionein. In a continuous labeling experiment the rate of synthesis of metallothionein reached a steady state after about 4 h, in response to either inducer. The lag period was identical for both dexamethasone and Zn2+, with similarly shaped induction curves. Induction by dexamethasone, but not by Zn2+, was inhibited by progesterone. Zn2+ and dexamethasone appear to induce metallothionein synthesis in HeLa cells by mechanisms independent of one another.
在无血清培养基中生长的HeLa细胞中，金属硫蛋白可由Zn2+和地塞米松诱导产生。地塞米松能够在几乎无锌的培养基（[Zn2+]=0.01微摩尔）中诱导HeLa细胞合成金属硫蛋白。地塞米松的存在不会改变Zn2+诱导金属硫蛋白的剂量/反应曲线，这进一步表明这两种诱导剂通过独立的机制发挥作用。地塞米松在24小时内可使Zn2+摄取量增加1.7倍。然而，在最初的4小时内Zn2+摄取量没有增加。相比之下，在接触任何一种诱导剂后的4小时内，对Zn2+或地塞米松作出反应的金属硫蛋白合成都清晰可见。在24小时观察到的细胞内65Zn2+含量增加完全是由于与金属硫蛋白结合的金属水平升高所致。在连续标记实验中，无论对哪种诱导剂作出反应，金属硫蛋白的合成速率在约4小时后达到稳定状态。地塞米松和Zn2+的延迟期相同，诱导曲线形状相似。地塞米松诱导作用（而非Zn2+诱导作用）受到孕酮的抑制。Zn2+和地塞米松似乎通过彼此独立的机制诱导HeLa细胞合成金属硫蛋白。
