Anemia of the Belgrade rat: evidence for defective membrane transport of iron.
The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with 59Fe and 125I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect.
D000740:Anemia / Q000503:physiopathology*; D000818:Animals; D001692:Biological Transport; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D006427:Hemin / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D007504:Iron Radioisotopes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains / Q000097:blood / Q000235:genetics*; D011990:Receptors, Transferrin / Q000502:physiology; D012156:Reticulocytes / Q000378:metabolism / Q000648:ultrastructure*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism
D007457:Iodine Radioisotopes; D007504:Iron Radioisotopes; D011990:Receptors, Transferrin; D014168:Transferrin; D006427:Hemin; D007501:Iron; D013755:Tetradecanoylphorbol Acetate