Aluminum inhibits hemoglobin synthesis but enhances iron uptake in Friend erythroleukemia cells.
Aluminum (Al) overload in dialysis patients and experimental animals is associated with the development of anemia. However, the precise mechanisms of erythrocyte Al uptake and toxicity are poorly understood. Al accumulation, hemoglobin (Hb) synthesis and cell growth were evaluated in dimethylsulfoxide (DMSO)-induced Friend erythroleukemia cells (FEC), a model system for erythroid differentiation. FEC were grown in media containing either Al citrate, transferrin-aluminum (Tf-Al), Tf or no additions. Al accumulation occurring only in cells grown in Tf-Al containing media was detected at 24 hours and increased linearly up to 96 hours after induction. By 96 hours, 200 +/- 36 micrograms Al/liter lysed cells were detected in Tf-Al grown cells versus 5 +/- 1 micrograms Al/liter lysed cells in cells grown in Al citrate (P less than 0.001). Tf-Al inhibited Hb synthesis at 72 hours after induction. At 96 hours 50 +/- 15% cells were benzidine positive when grown in Tf-Al compared to 76 +/- 15% in Al citrate (P less than 0.001). FEC grown in increasing concentrations of Tf-Al (100 to 500 micrograms/ml) showed inhibition of Hb synthesis at lower concentrations of Tf-Al at 100 micrograms/ml than for cell growth at 300 micrograms/ml. Higher concentrations of Tf-Al (greater than 300 micrograms/ml) did not further inhibit Hb synthesis or cell growth. Iron (Fe) and Tf uptake were increased in Al loaded FEC compared to control cells. The increased Tf uptake was probably the result of increased Tf receptor expression on FES since Tf cell cycling time was unchanged. These data indicate that Al utilizes the Tf uptake pathway for entry into erythrocyte precursors. Al is toxic at sites distal to Fe uptake, possibly at the heme and/or globin synthetic pathways, resulting in decreased Hb synthesis and cell growth.
Abreo
K
K
Department of Medicine, Louisiana State University Medical Center, Shreveport.
Glass
J
J
Sella
M
M
D000535:Aluminum / Q000493:pharmacokinetics / Q000494:pharmacology*; D000748:Anemia, Macrocytic / Q000139:chemically induced; D001927:Brain Diseases / Q000139:chemically induced; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D010018:Osteomalacia / Q000139:chemically induced
D006454:Hemoglobins; D000535:Aluminum; D007501:Iron; D004121:Dimethyl Sulfoxide