Sone T, Yamaoka K, Minami Y, Tsunoo H
J Biol Chem. 1987 Apr 25;262(12):5878-85.
A study was carried out on the uptake of copper, zinc, or cadmium ions and their induction of metallothionein synthesis in Menkes' and normal lymphoblastoid cells. The main difference between Menkes' and normal cells in the uptake of these metal ions was an increased uptake of copper ions in Menkes' cells at a low concentration of CuCl2 (2.1 microM). The CuCl2 concentration necessary to induce metallothionein synthesis in Menkes' cells was 50 microM, whereas that in normal cells was about 200 microM. The levels of zinc or cadmium ions needed to induce metallothionein in Menkes' cells were similar to those in normal cells. At least four isomers of metallothionein were induced by copper, zinc, and cadmium ions in both types of cells. Metallothionein synthesis in Menkes' and normal cells was induced when the amounts of intracellular copper reached a threshold level of approximately 0.2 nmol/10(6) cells, and the rate of metallothionein synthesis in these cells was increased as a function of the amounts of intracellular copper (0.2-1.7 nmol/10(6) cells). These results indicate that the induction of metallothionein synthesis in lymphoblastoid cells is controlled by the level of intracellular copper, suggesting that the major defect in Menkes' cells is not due to the abnormal regulation of metallothionein synthesis but to an alteration of the copper metabolism in cells by which the levels of intracellular copper become larger than those in normal cells and just lower than the threshold level for induction of metallothionein synthesis.
一项关于铜、锌或镉离子摄取及其在门克斯病和正常淋巴母细胞中诱导金属硫蛋白合成的研究得以开展。门克斯病细胞和正常细胞在摄取这些金属离子方面的主要差异在于，在低浓度氯化铜（2.1微摩尔）时，门克斯病细胞对铜离子的摄取增加。在门克斯病细胞中诱导金属硫蛋白合成所需的氯化铜浓度为50微摩尔，而在正常细胞中约为200微摩尔。在门克斯病细胞中诱导金属硫蛋白所需的锌或镉离子水平与正常细胞中的相似。在这两种类型的细胞中，铜、锌和镉离子均诱导出至少四种金属硫蛋白异构体。当细胞内铜的量达到约0.2纳摩尔/10⁶个细胞的阈值水平时，门克斯病细胞和正常细胞中的金属硫蛋白合成被诱导，并且这些细胞中金属硫蛋白合成的速率随着细胞内铜的量（0.2 - 1.7纳摩尔/10⁶个细胞）而增加。这些结果表明，淋巴母细胞中金属硫蛋白合成的诱导受细胞内铜水平的控制，这表明门克斯病细胞中的主要缺陷并非由于金属硫蛋白合成的异常调节，而是由于细胞内铜代谢的改变，通过这种改变，细胞内铜的水平变得高于正常细胞且刚好低于诱导金属硫蛋白合成的阈值水平。
