Mobilization of ferritin iron in erythroblasts by chelating agents.
Intracellular ferritin in newt (Triturus cristatus) erythroblasts was accessible to the chelating effects of EDTA and pyridoxal phosphate. EDTA (0.5-1 mM) promoted release of radioactive iron from ferritin of pulse-labelled erythroblasts during chase incubation, but its continuous presence was not necessary for ferritin iron mobilization. Brief exposure to EDTA was sufficient to release 60-70% of ferritin 59Fe content during ensuing chase in EDTA-free medium. EDTA also suppressed cellular iron uptake and utilization for heme synthesis, but these activities were restored upon its removal. Pyridoxal-5'-phosphate (0.5-5 mM) also stimulated loss of radioactive iron from ferritin; however, ferritin iron release by pyridoxal phosphate required its continued presence. Unlike EDTA, pyridoxal phosphate did not interfere with iron uptake or its utilization for heme synthesis. Chelator-mobilized ferritin iron accumulated initially in the hemolysate as a low-molecular-weight component and appeared to be eventually released into the medium. No radioactive ferritin was found in the medium of chelator-treated cells, indicating that secretion or loss of ferritin was not responsible for decreasing cellular ferritin 59Fe content. Moreover, there was no transfer of radioactive iron between the low-molecular-weight component released into the medium and plasma transferrin. These results indicate that chelator-released ferritin iron is not available for cellular utilization in heme synthesis and that ferritin iron released by this process is not an alternative or complementary iron source for heme synthesis. Correlation of these data with effects of succinylacetone inhibition of heme synthesis and with previous studies indicates that the main role of erythroid cell ferritin is absorption and storage of excess iron not used for heme synthesis.
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D004900:Erythroblasts / Q000187:drug effects* / Q000378:metabolism; D005293:Ferritins / Q000097:blood*; D006537:Heptanoates / Q000494:pharmacology; D066298:In Vitro Techniques; D007501:Iron / Q000097:blood*; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D014319:Triturus
D002614:Chelating Agents; D006537:Heptanoates; C020804:succinylacetone; D011732:Pyridoxal Phosphate; D005293:Ferritins; D004492:Edetic Acid; D007501:Iron