Nartey N O, Frei J V, Cherian M G
Department of Pathology, University of Western Ontario, London, Canada.
Lab Invest. 1987 Oct;57(4):397-401.
Wilson's disease is a rare inherited disorder of copper (Cu) metabolism characterized by the deposition of Cu in the liver, brain, and cornea. The levels of metallothionein (MT), Cu, and zinc (Zn) in the livers of two Wilson's disease patients were analyzed in this study. About 50-fold increase in the Cu levels above normal controls was observed in both patients (160 and 298 micrograms/g of wet tissue). About 73% of subcellular Cu was present in the cytoplasmic fraction and most of it was in association with MT. Analysis of hepatic MT levels showed a 3-fold increase (863 micrograms/g of wet tissue) over control human levels (321 micrograms/g of wet tissue). The two forms of MT (MT-I and MT-II) were isolated from one liver sample. Both forms contained high amounts of Cu (11 to 12 g atoms/mole), indicating saturation of MT which had only 2 to 3 g atoms of zinc. The distribution of MT in the hepatocytes was investigated using an immunohistochemical method. In tissue sections with minimal tissue damage, there was intense cytoplasmic staining for MT in hepatocytes whereas both nuclear and cytoplasmic staining was found in tissue sections with extensive necrosis and fibrosis. These results suggest that MT is the major hepatic Cu-binding protein in Wilson's disease, that it is present in a form saturated with Cu, and that only in degenerating hepatocytes is it found in the nucleus as well as the cytoplasm.
威尔逊氏病是一种罕见的遗传性铜（Cu）代谢紊乱疾病，其特征是铜在肝脏、大脑和角膜中沉积。本研究分析了两名威尔逊氏病患者肝脏中的金属硫蛋白（MT）、铜和锌（Zn）水平。两名患者的铜水平均比正常对照高出约50倍（湿组织中为160和298微克/克）。亚细胞铜的约73%存在于细胞质部分，且大部分与金属硫蛋白结合。肝脏MT水平分析显示，与正常人体水平（321微克/克湿组织）相比增加了3倍（863微克/克湿组织）。从一个肝脏样本中分离出了两种形式的金属硫蛋白（MT-I和MT-II）。两种形式都含有大量的铜（11至12克原子/摩尔），表明金属硫蛋白已饱和，而其锌含量仅为2至3克原子。使用免疫组织化学方法研究了金属硫蛋白在肝细胞中的分布。在组织损伤最小的切片中，肝细胞的细胞质对金属硫蛋白有强烈染色，而在有广泛坏死和纤维化的组织切片中，细胞核和细胞质均有染色。这些结果表明，金属硫蛋白是威尔逊氏病中主要的肝脏铜结合蛋白，它以铜饱和的形式存在，并且只有在退化的肝细胞中才会在细胞核和细胞质中都被发现。
