Suárez N, Eriksson H
Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
J Neurochem. 1993 Jul;61(1):127-31. doi: 10.1111/j.1471-4159.1993.tb03546.x.
Exposure to manganese compounds often occurs as the result of industrial production or mining. Although manganese appears in traces in animal and human tissue and is essential to certain biological processes, it is also toxic. In humans and animals, toxicity is mainly associated with the nervous system. The mechanism underlying behavioral and biochemical alterations observed after manganese intoxication is not fully understood. We have shown that the manganese present in serum after exposure to manganese oxide is bound to transferrin as trivalent manganic ion. In this study of manganese uptake and storage we used a clone of human neuroblastoma cells (SHSY5Y). These cells differentiate and express catecholaminergic properties. Saturation binding analysis of the transferrin-manganese complex to the cells revealed a single class of binding sites, with an apparent KD of 13 +/- 1 nM and a density of 11,000 +/- 2,000 binding sites per cell. The complex was internalized in a temperature-dependent way and reached saturation after 2 h when approximately 2% of the added manganese had been internalized. About 80% of the internalized manganese was found in ferritin after 24 h of exposure. The results demonstrate that the transferrin receptor on SHSY5Y cells can bind and internalize a manganese-transferrin complex as efficiently as an iron-transferrin complex, although a saturation of the manganese uptake was achieved.
接触锰化合物通常是工业生产或采矿的结果。尽管锰在动物和人体组织中以痕量形式存在，并且对某些生物过程至关重要，但它也是有毒的。在人和动物中，毒性主要与神经系统有关。锰中毒后观察到的行为和生化改变的潜在机制尚未完全了解。我们已经表明，接触氧化锰后血清中的锰以三价锰离子的形式与转铁蛋白结合。在这项关于锰摄取和储存的研究中，我们使用了人神经母细胞瘤细胞（SHSY5Y）的一个克隆。这些细胞会分化并表现出儿茶酚胺能特性。转铁蛋白 - 锰复合物与细胞的饱和结合分析显示出一类单一的结合位点，其表观解离常数（KD）为13±1 nM，每个细胞的结合位点密度为11,000±2,000个。该复合物以温度依赖的方式被内化，在2小时后达到饱和，此时约2%添加的锰已被内化。暴露24小时后，约80%内化的锰存在于铁蛋白中。结果表明，SHSY5Y细胞上的转铁蛋白受体能够像铁 - 转铁蛋白复合物一样有效地结合和内化锰 - 转铁蛋白复合物，尽管锰的摄取达到了饱和。
