Dissociation of iron transport and heme biosynthesis from commitment to terminal maturation of murine erythroleukemia cells.
Treatment of murine erythroleukemia (MEL) cells with imidazole in the presence of dimethyl sulfoxide (Me2SO) has been shown to dissociate hemoglobin accumulation from commitment to terminal maturation. To explore the mechanism(s) of this effect, we studied iron transport and heme and hemoglobin synthesis in Me2SO-induced MEL cells that were then exposed to imidazole. Imidazole treatment (i) causes moderate inhibition of 125I-labeled transferrin binding to both control and Me2SO-treated MEL cells; (ii) markedly suppresses Me2SO-induced activation of iron uptake into MEL cells; (iii) markedly decreases the incorporation of iron into ferritin; and (iv) abolishes heme biosynthesis from [2-14C]glycine and hemoglobin accumulation in Me2SO-treated cells. Imidazole treatment does not inhibit other aspects of cellular maturation; cells treated with Me2SO in the presence or absence of imidazole exhibit similar changes in proliferative activity and protein synthesis and, as shown previously, in cell morphology. Inhibition of hemoglobin accumulation in MEL cells is reversible on withdrawal of imidazole but is not altered by exogenous hemin. These data indicate that commitment to terminal maturation is regulated independently from the systems for iron transport and heme biosynthesis during early phases of erythroid cell differentiation.
D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006418:Heme / Q000096:biosynthesis* / Q000494:pharmacology; D006454:Hemoglobins / Q000235:genetics; D007093:Imidazoles / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D007942:Leukemia, Experimental / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism; D011990:Receptors, Transferrin; D014168:Transferrin / Q000378:metabolism
D006454:Hemoglobins; D007093:Imidazoles; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin; D006418:Heme; C029899:imidazole; D007501:Iron; D004121:Dimethyl Sulfoxide