Ferritin Synthesis in Developing Erythroid Precursor Cells

AbstractThe effect of maturation on ferritin synthesis in erythroid precursor cells was studied in vitro in a population of rabbit bone marrow cells synchronized by actinomycin D. Undifferentiated hemopoietic stem cells were compared with orthochromatic normoblasts and reticulocytes, following incubation in Krebs-Ringer phosphate buffer containing 40% normal rabbit serum. Apoferritin synthesis was measured by following the incorporation of [3H]amino acids into purified ferritin and was correlated with the rate of total protein synthesis and with the rate of radioiron uptake by whole cells and its incorporation into heme. With increasing cellular maturation, a progressive reduction in both apoferritin and total protein synthesis was observed, with undifferentiated cells synthesizing 12 times more protein and ferritin than reticulocytes. The rate of ferritin synthesis was inversely related to the rate of radioiron uptake by whole cells and radioiron incorporation into heme; the lowest rates of radioiron uptake and heme synthesis were found in undifferentiated cells, and the highest rates were in reticulocytes. Radioiron incorporation into ferritin was higher in orthochromatic normoblasts than in undifferentiated cells, but was very low in reticulocytes. This sequence of events indicates that in developing erythroid precursor cells, ferritin synthesis precedes the synthesis of hemoglobin and provides an intracellular storage compartment for the supply of iron for subsequent incorporation into newly formed hemoglobin.