Waldrop G L, Ettinger M J
Department of Biochemistry, State University of New York, Buffalo 14214.
Biochem J. 1990 Apr 15;267(2):417-22. doi: 10.1042/bj2670417.
Fibroblasts from the brindled mouse model of Menkes disease are known to accumulate excess copper. Most of the copper in the cytosol of these fibroblasts is bound to metallothionein (MT), which is elevated in Menkes or brindled mouse fibroblasts. Copper accumulation by normal fibroblasts containing excess MT was examined to determine if the excess copper accumulation phenotype was secondary to excess MT or associated with the primary defect in fibroblasts from the brindled mice. MT was induced in normal fibroblasts by copper, zinc or dexamethasone to levels comparable with those in brindled mice fibroblasts, as determined by radioimmunoassays. Normal fibroblasts containing excess MT accumulate copper normally, i.e. they do not exhibit the excess copper accumulation phenotype. Consistent with this result, copper efflux from normal fibroblasts containing excess MT was also normal. The data suggest that one function of the protein associated with the primary defect is to help determine how much copper is taken up and retained by fibroblasts and other cell types exhibiting the excess copper phenotype in Menkes disease. The capacity of this protein is apparently exceeded in normal fibroblasts if serum or albumin is not present extracellularly to limit total copper uptake. Consistent with a defect in an intracellular protein, the kinetics of copper transport by brindled mice fibroblasts were found to be normal.
已知来自门克斯病（Menkes disease）的斑驳小鼠模型的成纤维细胞会积累过量的铜。这些成纤维细胞胞质溶胶中的大部分铜与金属硫蛋白（MT）结合，而金属硫蛋白在门克斯病或斑驳小鼠的成纤维细胞中含量升高。研究了含有过量MT的正常成纤维细胞的铜积累情况，以确定过量铜积累表型是MT过量的继发结果，还是与斑驳小鼠成纤维细胞的原发性缺陷相关。通过放射免疫测定法测定，用铜、锌或地塞米松诱导正常成纤维细胞中的MT至与斑驳小鼠成纤维细胞相当的水平。含有过量MT的正常成纤维细胞正常积累铜，即它们不表现出过量铜积累表型。与该结果一致，含有过量MT的正常成纤维细胞的铜流出也正常。数据表明，与原发性缺陷相关的蛋白质的一个功能是帮助确定成纤维细胞和门克斯病中表现出过量铜表型的其他细胞类型摄取和保留多少铜。如果细胞外不存在血清或白蛋白以限制总铜摄取，正常成纤维细胞中这种蛋白质的能力显然会被超过。与细胞内蛋白质缺陷一致，发现斑驳小鼠成纤维细胞的铜转运动力学是正常的。
