Rubin A H, Terasaki M, Sanui H
Proc Natl Acad Sci U S A. 1979 Aug;76(8):3917-21. doi: 10.1073/pnas.76.8.3917.
Omission of Ca(2+) from the medium of confluent BALB/c3T3 cells for a period of 17 hr causes a large decrease in the number of cells synthesizing DNA. This effect is reversed by raising the Mg(2+) concentration of the medium to 20 mM. However, if the [Mg(2+)] is greater than 20 mM ("ultra-high" Mg(2+)), there is again a decrease in the number of cells synthesizing DNA. The synthesis of protein has a similar dependence on Mg(2+) concentration in Ca(2+)-deficient medium, but it responds within 45 min of the shift in cation concentrations rather than the 10 hr that is required for the change in DNA synthesis to become apparent. Cells in the ultrahigh Mg(2+) concentrations that are at first inhibitory to protein synthesis later return to maximal protein synthesis. This delayed increase in protein synthesis is reflected in a delayed increase in DNA synthesis. Intracellular concentrations of Mg(2+) in Ca(2+)-deficient media increase in proportion to extracellular Mg(2+) concentrations. Cells in medium with 30 mM Mg(2+) have a high intracellular content of Mg(2+) at 3 hr but have decreased their intracellular content by 17 hr, a time at which protein synthesis has been restored to normal. Intracellular Na(+) and K(+) concentrations also change in Ca(2+)-deficient medium, but independent variation of these ions shows that protein synthesis is relatively insensitive to their concentration. Intracellular Ca(2+) remains fairly constant under all these conditions. The rate of protein synthesis of intact cells changes as a function of intracellular Mg(2+) content in a manner very similar to that which has been reported for cell-free systems. We conclude that protein synthesis is very sensitive to small changes in intracellular [Mg(2+)] within physiological range and that the onset of DNA synthesis is dependent on the rate of protein synthesis. Regulation of the availability of Mg(2+) within the cell therefore presents a plausible mechanism for growth control.
在汇合的BALB/c3T3细胞培养基中去除Ca(2+) 17小时会导致合成DNA的细胞数量大幅减少。将培养基中的Mg(2+)浓度提高到20 mM可逆转这种效应。然而，如果[Mg(2+)]大于20 mM（“超高”Mg(2+)），合成DNA的细胞数量会再次减少。在缺钙培养基中，蛋白质合成对Mg(2+)浓度有类似的依赖性，但它在阳离子浓度变化后45分钟内就会做出反应，而DNA合成变化明显则需要10小时。处于超高Mg(2+)浓度下最初抑制蛋白质合成的细胞，随后会恢复到最大蛋白质合成水平。蛋白质合成的这种延迟增加反映在DNA合成的延迟增加上。缺钙培养基中细胞内Mg(2+)的浓度与细胞外Mg(2+)浓度成比例增加。在含有30 mM Mg(2+)的培养基中的细胞在3小时时细胞内Mg(2+)含量较高，但在17小时时其细胞内含量下降，此时蛋白质合成已恢复正常。细胞内Na(+)和K(+)浓度在缺钙培养基中也会发生变化，但这些离子的独立变化表明蛋白质合成对其浓度相对不敏感。在所有这些条件下，细胞内Ca(2+)保持相当恒定。完整细胞的蛋白质合成速率随细胞内Mg(2+)含量的变化而变化，其方式与无细胞系统中报道的非常相似。我们得出结论，蛋白质合成对生理范围内细胞内[Mg(2+)]的微小变化非常敏感，并且DNA合成的开始取决于蛋白质合成的速率。因此，细胞内Mg(2+)可用性的调节为生长控制提供了一种合理的机制。
