Abreo K, Abreo F, Sella M L, Jain S
Department of Medicine, Louisiana State University University Medical Center, Shreveport 71130, USA.
J Neurochem. 1999 May;72(5):2059-64. doi: 10.1046/j.1471-4159.1999.0722059.x.
Aluminum (Al) and iron (Fe) have been implicated as playing a toxic role in the pathologic lesions of Alzheimer's disease. In the following report we describe the uptake and toxicity of Al, the effect of Al on Fe uptake, and the expression of neurofibrillary tangle (NFT) protein in murine neuroblastoma cells (Neuro 2A). Significant cell Al uptake and inhibition of cell growth were seen in Neuro 2A cells at 24, 48, 72, and 96 h after plating in medium containing Al transferrin (Al-Tf) and Al citrate. Al-loaded Neuro 2A cells showed increased rates of 59Fe and 125I-Tf uptake and total cellular Fe content at 24, 48, 72, and 96 h after plating compared with control cultures. Significant increases in NFT protein staining were detected in Al-exposed cells at 72 and 96 h in culture compared with controls. The intensity of NFT staining in Al-loaded cells was directly proportional to the time in culture. There was no difference in malonyldialdehyde levels measured in control versus Al-loaded Neuro 2A cells. These results suggest that the accumulation of Al in Neuro 2A cells resulted in increased uptake of Fe, inhibition of cell growth, and expression of NFT protein, partially mimicking the pathological hallmarks of Alzheimer's disease. This model system may also be applicable for Al-induced dialysis dementia, because the Al concentrations at which cell toxicity occurred can be found in dialysis patients.
铝（Al）和铁（Fe）被认为在阿尔茨海默病的病理损伤中发挥着毒性作用。在以下报告中，我们描述了铝的摄取和毒性、铝对铁摄取的影响以及神经纤维缠结（NFT）蛋白在小鼠神经母细胞瘤细胞（Neuro 2A）中的表达。在接种于含有铝转铁蛋白（Al-Tf）和柠檬酸铝的培养基中的Neuro 2A细胞中，在接种后24、48、72和96小时观察到显著的细胞铝摄取和细胞生长抑制。与对照培养物相比，负载铝的Neuro 2A细胞在接种后24、48、72和96小时显示出59Fe和125I-Tf摄取率及细胞总铁含量增加。与对照相比，在培养72和96小时的铝暴露细胞中检测到NFT蛋白染色显著增加。负载铝的细胞中NFT染色强度与培养时间成正比。对照Neuro 2A细胞和负载铝的Neuro 2A细胞中测得的丙二醛水平没有差异。这些结果表明，铝在Neuro 2A细胞中的积累导致铁摄取增加、细胞生长抑制和NFT蛋白表达，部分模拟了阿尔茨海默病的病理特征。该模型系统也可能适用于铝诱导的透析性痴呆，因为在透析患者中可以发现发生细胞毒性的铝浓度。
