Erythropoietin control of terminal erythroid differentiation: maintenance of cell viability, production of hemoglobin, and development of the erythrocyte membrane.
Using the spleen cells of mice infected with the anemia-inducing strain of Friend leukemia virus, an in vitro model system of erythropoiesis has been developed in which a homogeneous population of murine proerythroblasts terminally differentiates in response to erythropoietin (EP). The biochemical events involved in EP's capacity to maintain viability, induce hemoglobin production, and promote the development of the specialized erythrocyte membrane were studied during the 48-72 hour period required for proerythroblasts to differentiate into reticulocytes. The results show that EP increases glucose uptake and the syntheses of RNA and protein in the first few hours after exposure of the erythroblasts to the hormone. A coordinated production of heme, alpha and beta globin occurs later and peaks at about 48 hours. This peak corresponds to the time at which the majority of cells are undergoing enucleation and becoming reticulocytes. The syntheses of the erythrocyte membrane and membrane skeletal proteins are not coordinated, and multiple patterns of synthesis are found with respect to the time of EP exposure. A number of proteins are lost from the membrane fraction while the characteristic proteins of the mature erythrocyte become prominent in the membrane fraction of erythroid cells as they develop from reticulocytes into erythrocytes.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004900:Erythroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004905:Erythrocyte Aging; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D005622:Friend murine leukemia virus; D006454:Hemoglobins / Q000096:biosynthesis*; D004915:Leukemia, Erythroblastic, Acute / Q000503:physiopathology*; D007942:Leukemia, Experimental / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012156:Reticulocytes / Q000473:pathology; D013154:Spleen / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D006454:Hemoglobins; D004921:Erythropoietin