Aluminum alters the compartmentalization of iron in Friend erythroleukemia cells.
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)
Abreo
K
K
Department of Medicine, Louisiana State University Medical Center, Shreveport.
Glass
J
J
Jain
S
S
Sella
M
M
D000535:Aluminum / Q000633:toxicity*; D005293:Ferritins / Q000378:metabolism; D005622:Friend murine leukemia virus; D006801:Humans; D007501:Iron / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D015227:Lipid Peroxidation; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D005293:Ferritins; D000535:Aluminum; D007501:Iron