Abreo K, Glass J, Jain S, Sella M
Department of Medicine, Louisiana State University Medical Center, Shreveport.
Kidney Int. 1994 Mar;45(3):636-41. doi: 10.1038/ki.1994.85.
Aluminum (Al) accumulation in renal failure patients can result in encephalopathy, osteomalacia, and anemia. Since the cellular mechanisms of Al toxicity are not completely understood we used cultured Friend erythroleukemia cells (FEC) as a model system of Al-induced anemia. In this system Al accumulation leads to decreased cell growth and hemoglobin synthesis despite increased iron (Fe) uptake by transferrin (Tf) endocytosis. In FEC we evaluated the effect of Al on the cellular and subcellular accumulation of Fe, ferritin concentration, the uptake of Fe by ferritin, the exit of cellular Fe, and membrane lipid peroxidation. FEC were grown in media with or without the addition of Al-Tf and studies were done at 24, 48, 72, and 96 hours after plating. The highest concentration of intracellular Al was found in mitochondria with lesser amounts in the nucleus, and the least was in cytosol. The rate of Fe uptake was higher in Al-loaded FEC without a proportionally increased rate of exit. This resulted in higher concentrations of Fe in Al-loaded FEC. Subcellular fractionation following the uptake of 59Fe, 125I-Tf in Al-loaded FEC showed increased uptake of 59Fe in the nuclear and mitochondrial compartments with no increase in the cytosol. Al-loaded FEC showed decreased ferritin content and decreased uptake of 59Fe by ferritin. Increased membrane lipid peroxidation occurred in Al-loaded FEC at 96 hours as assessed by cellular malonyldialdehyde accumulation. These results indicate that Al disrupts Fe metabolism in FEC by increasing cellular Fe content with increased compartmentalization of Fe in the mitochondria and nuclei, decreased ferritin content, and decreased uptake of Fe by ferritin.(ABSTRACT TRUNCATED AT 250 WORDS)
肾衰竭患者体内铝（Al）蓄积可导致脑病、骨软化症和贫血。由于铝毒性的细胞机制尚未完全明确，我们使用培养的Friend红白血病细胞（FEC）作为铝诱导贫血的模型系统。在该系统中，尽管转铁蛋白（Tf）通过内吞作用摄取的铁（Fe）增加，但铝蓄积仍导致细胞生长和血红蛋白合成减少。在FEC中，我们评估了铝对铁的细胞和亚细胞蓄积、铁蛋白浓度、铁蛋白对铁的摄取、细胞内铁的外流以及膜脂质过氧化的影响。FEC在添加或不添加铝 - 转铁蛋白的培养基中生长，并在接种后24、48、72和96小时进行研究。细胞内铝浓度最高的部位是线粒体，细胞核中含量较少，细胞质中最少。铝负载的FEC中铁摄取速率较高，但铁外流速率没有相应成比例增加。这导致铝负载的FEC中铁浓度更高。在铝负载的FEC中摄取59Fe、125I - Tf后的亚细胞分级分离显示，细胞核和线粒体部分对59Fe的摄取增加，而细胞质中没有增加。铝负载的FEC显示铁蛋白含量降低，铁蛋白对59Fe的摄取减少。通过细胞丙二醛蓄积评估，铝负载的FEC在96小时时膜脂质过氧化增加。这些结果表明，铝通过增加细胞内铁含量、增加铁在线粒体和细胞核中的分隔、降低铁蛋白含量以及减少铁蛋白对铁的摄取，扰乱了FEC中的铁代谢。（摘要截断于250字）
