Biomaterial Database

Role of nonhemoglobin heme accumulation in the terminal differentiation of Friend erythroleukemia cells. 1981

S C Lo, and R Aft, and G C Mueller

The differentiation of murine erythroleukemia cells (T3C12 Friend cells) on treatment with dimethyl sulfoxide (DMSO) has been correlated with an early and extended overproduction of heme. The cessation of cell replication and the development of nuclear condensation, changes which are associated with the terminal differentiation of these cells, occur when the level of heme rises 0.1 nmol/10(6) cells over that amount which can be complexed by globin protein. A significant fraction of the excess heme is localized in the nuclei of the DMSO-treated cells. The addition of exogenous hemin facilitates the onset of terminal differentiation in the DMSO-treated T3C12 cells, whereas only the induction of globin gene expression is observed in the absence of DMSO. To study the role of heme in erythroid differentiation, a Friend cell variant (R10) has been isolated whose synthesis and accumulation of heme in response to DMSO is deficient. This variant grows logarithmically in the presence of DMSO and fails to terminally differentiate. When exogenous hemin is added, the DMSO-treated R10 cells stop replicating. In the absence of DMSO, however, hemin-treated R10 cells continue to grow and express their globin genes without exhibiting other signs of terminal differentiation. The combined results support the conclusion that both the DMSO treatment and the accumulation of excess heme are required to bring about the terminal differentiation of Friend erythroleukemia cells. Preliminary evidence is presented which suggests that in addition to the induction of heme and globin synthesis, DMSO also induces a heme activation process which is required for differentiation. The possible relationship of this process to the terminal differentiation of erythroid cells is discussed.

UI	MeSH Term	Description	Entries
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002467	Cell Nucleus	Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)	Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004121	Dimethyl Sulfoxide	A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.	DMSO,Dimethyl Sulphoxide,Dimethylsulfoxide,Dimethylsulphinyl,Dimethylsulphoxide,Dimexide,Rheumabene,Rimso,Rimso 100,Rimso-50,Sclerosol,Sulfinylbis(methane),Rimso 50,Rimso50,Sulfoxide, Dimethyl,Sulphoxide, Dimethyl
D004915	Leukemia, Erythroblastic, Acute	A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.	Di Guglielmo's Disease,Erythremic Myelosis,Erythroblastic Leukemia, Acute,Erythroleukemia,Leukemia, Myeloid, Acute, M6,Myeloid Leukemia, Acute, M6,Di Guglielmo Disease,Acute Erythroblastic Leukemia,Acute Erythroblastic Leukemias,Di Guglielmos Disease,Disease, Di Guglielmo,Disease, Di Guglielmo's,Erythremic Myeloses,Erythroblastic Leukemias, Acute,Erythroleukemias,Leukemia, Acute Erythroblastic,Leukemias, Acute Erythroblastic,Myeloses, Erythremic,Myelosis, Erythremic
D004920	Erythropoiesis	The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.	Erythropoieses
D005622	Friend murine leukemia virus	A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.	Friend Virus,Rowson-Parr Virus,Rowson Parr Virus,Virus, Friend,Virus, Rowson-Parr
D005914	Globins	A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.	Globin
D006418	Heme	The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.	Ferroprotoporphyrin,Protoheme,Haem,Heme b,Protoheme IX
D006427	Hemin	Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen.	Ferriprotoporphyrin,Hematin,Alkaline Hematin D-575,Chlorohemin,Ferrihaem,Ferriheme Chloride,Ferriprotoporphyrin IX,Ferriprotoporphyrin IX Chloride,Panhematin,Protohemin,Protohemin IX,Alkaline Hematin D 575,Chloride, Ferriheme,Chloride, Ferriprotoporphyrin IX,Hematin D-575, Alkaline