Specific binding of erythropoietin to its receptor on responsive mouse erythroleukemia cells.

Todokoro, Kazuo; Kanazawa, Susumu; Arima, Hiroshi; Ikawa, Yoji

doi:10.1073/pnas.84.12.4126

Cited by 96 publications

(31 citation statements)

References 25 publications

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“…These data provide the evidence for crosstalk between TNF/TNFR1 and EPOR to coordinate the onset of angiogenesis in cerebral endothelial cells. The EPO evokes its biological function through interaction with its receptor EPOR (Todokoro et al, 1987). Cerebral endothelial cells express EPOR that has 10 times higher affinity to EPO (2 nmol/L) than EPOR in neurons (20 nmol/L) (Brines and Cerami, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The EPO has been shown to have neuroprotective and neurorestorative effects after stroke (Ruscher et al, 2002;Wang et al, 2004a). Administration of recombinant human EPO (rhEPO) promotes interaction with the EPO receptor (EPOR) and augments angiogenesis and neurogenesis in the ischemic brain (Liu et al, 2008;Todokoro et al, 1987;Wang et al, 2004a, b). Mechanisms underlying exogenous EPO-enhanced angiogenesis have not been investigated in the brain.…”

Section: Introductionmentioning

confidence: 99%

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Tumor Necrosis Factor α Primes Cerebral Endothelial Cells for Erythropoietin-Induced Angiogenesis

Wang

Chopp

Hua³

et al. 2010

J Cereb Blood Flow Metab

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Erythropoietin (EPO) enhances angiogenesis in the ischemic brain. Stroke induces secretion of tumor necrosis factor a (TNF-a). We investigated the effect of TNF-a on EPO-induced in vitro angiogenesis in cerebral endothelial cells. Using a capillary-like tubular formation assay, we found that transient incubation of primary rat cerebral microvascular endothelial cells (RECs) with TNF-a substantially upregulated EPO receptor (EPOR) expression and addition of EPO into TNF-a-treated RECs significantly augmented the capillary-like tube formation. Blockage of TNF receptor 1 (TNFR1) suppressed TNF-a-upregulated EPOR expression and abolished EPO-induced tube formation. Attenuation of endogenous EPOR with small interfering RNA (siRNA) also inhibited EPO-enhanced tube formation. Treatment of RECs with EPO activated nuclear factor-kappa B (NF-jB) and Akt. Incubation of the TNF-a-treated endothelial cells with EPO activated vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), angiopoietin 1 (Ang1), and Tie2. Blockage of VEGFR2 and Tie2 resulted in reduction of EPO-augmented tube formation. These data indicate that interaction of TNF-a with TNFR1 sensitizes cerebral endothelial cells for EPO-induced angiogenesis by upregulation of EPOR, which amplifies the effect of EPO on activation of the VEGF/VEGFR2 and Ang1/Tie2 pathways. Our results provide the evidence for crosslink between TNF and EPOR to coordinate the onset of angiogenesis in cerebral endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumor Necrosis Factor α Primes Cerebral Endothelial Cells for Erythropoietin-Induced Angiogenesis

Wang

Chopp

Hua³

et al. 2010

J Cereb Blood Flow Metab

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“…Hence, exon 16 splicing pattern was examined in Rauscher cell lines, as well as in two MEL cell lines: SKT6 and 745-A. SKT6 is an SFFV MEL cell type that has the potential to differentiate in response to Epo (Todokoro et al, 1987), whereas the SFFV 745-A cells do not differentiate upon exposure to Epo. To ascertain that Epo potential activity is not altered in SFFV cell cultures, we performed a Northern blot analysis, using c-myc probe (not shown), and confirmed the early c-myc transcriptional activation in all three cell lines, as previously reported (Chern et al, 1991).…”

Section: Resultsmentioning

confidence: 99%

“…IW32 and NN10 are derived from F-MuLV-induced erythroleukemias. SKT6 is an Epo-responsive SFFV-derived cell line (Todokoro et al, 1987). Two Rauscher cell lines were tested; they derive from leukemic mice infected with Rauscher virus (Chern et al, 1991;Hanspal et al, 1992).…”

Section: Cell Culture Induction and Transfectionmentioning

confidence: 99%

Spi-1/PU.1 but not Fli-1 inhibits erythroid-specific alternative splicing of 4.1R pre-mRNA in murine erythroleukemia cells

Théoleyre

Deguillien²,

Morinière³

et al. 2003

Oncogene

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The inclusion of exon 16 in mature protein 4.1R mRNA arises from a stage-specific splicing event that occurs during late erythroid development. We have shown that mouse erythroleukemia (MEL) cells reproduce this erythroid-specific splicing event upon induction of differentiation. We here found that this splicing event is regulated specifically in erythroleukemic cells that have the potential to differentiate and produce hemoglobin, regardless of the nature of the differentiation inducer. Knowing that dysregulated expression of spi-1/pu.1 and fli-1 oncogenes is involved in MEL cell differentiation arrest, we looked at their effect on exon 16 erythroid splicing. We found that exon 16 inclusion requires Spi-1/ PU.1 shutdown in MEL cells, and that enforced expression of Spi-1/PU.1 inhibits exon selection, regardless of the presence or absence of a chemical inducer. By contrast, endogenous overexpression or enforced expression of Fli-1 has no effect on exon selection. We further showed that Spi-1/PU.1 acts similarly on the endogenous and on a transfected exon 16, suggesting a promoterindependent effect of Spi-1/PU.1 on splicing regulation. This study provides the first evidence that Spi-1/PU.1 displays the unique property, not shared with Fli-1, to inhibit erythroid-specific pre-mRNA splicing in erythroleukemia cell context.

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“…These cells provide a useful system for studying the molecular events occurring during erythropoietin receptor-mediated (and chemically induced) erythroid cell differentiation. We and others have characterized the membrane receptor molecules for erythropoietin on erythropoietin-responsive cells, i. e. on SKT6 cells [l 11, on mouse spleen cells infected with anemiainducing Friend virus complex [12] and on mouse fetal liver cells [13]. Very recently, cDNAs for mouse erythropoietin receptor were cloned and characterized [14,151.…”

mentioning

confidence: 99%

Transmembrane signaling during erythropoietin‐ and dimethylsulfoxide‐induced erythroid cell differentiation

Kuramochi¹,

Sugimoto²,

Ikawa³

et al. 1990

European Journal of Biochemistry

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Erythropoietin is a glycoprotein factor which specifically regulates the proliferation and differentiation of erythroid progenitor cells. We have investigated here the biochemical mechanisms of erythroid differentiation on mouse erythroleukemia SKT6 cells which can be induced to differentiate either with erythropoietin or dimethyl sulfoxide (Me,SO). CAMP-elevating agents, such as forskolin and 3-isobutyl-l-methyl-xanthine, caused spontaneous erythroid differentiation, and these agents showed the stimulatory effects on erythropoietin-or Me2SO-induced differentiation. An adenylate cyclase inhibitor, 2',5'-dideoxyadenosine, blocked erythropoietin-induced differentiation. The intracellular cAMP level was rapidly increased by addition of erythropoietin but not by Me2S0. These observations suggest that erythroid differentiation induced by erythropoietin is mediated, at least in part, through the CAMP-dependent pathway. When the effect of erythropoietin and Me2S0 on the intracellular Ca2+ level was examined using fura 2, no acute change was observed. Measurements of the levels of inositol1,4,5-trisphosphate and diacylglycerol following stimulation with erythropoietin or Me2S0 showed that phosphatidylinositol turnover did not change significantly after erythropoietin stimulation but decreased gradually after MezSO induction. Taken together, these results indicate that a complex signaling network including the CAMP-dependent pathway is involved in the erythroid differentiation process.Hemopoiesis is regulated by a set of specific glycoprotein factors that affect the program for proliferation and differentiation of progenitor cells [l]. Among these humoral factors, three glycoproteins specific for erythropoietic lineage have been identified by recombinant DNA technology, and their physiological functions have been clarified [2 -61. Interleukin 3 [2] and granulocyte-macrophage colony-stimulation factor [3, 41 stimulate the proliferation and differentiation of early erythroid progenitor cells. Erythropoietin acts on more mature erythroid progenitor cells and induces differentiation of the cells to mature erythrocytes [5 -71. Erythropoietin has been purified to homogeneity from the urine of a patient with aplastic anemia [7]. Clones of complementary and genomic DNA encoding the human and mouse erythropoietin were isolated [5,6,8, 91 and the primary structures of the protein and its sugar moieties have been determined [ 101.Study of the action of this hormone has been hampered partly by the lack of a sufficient number of homogeneous cells which fully respond to erythropoietin. Recently we established a mouse erythroleukemia cell line SKT6 which can be induced to differentiate with either natural inducer erythropoietin or Correspondence to K. Todokoro,

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Specific binding of erythropoietin to its receptor on responsive mouse erythroleukemia cells.

Cited by 96 publications

References 25 publications

Tumor Necrosis Factor α Primes Cerebral Endothelial Cells for Erythropoietin-Induced Angiogenesis

Tumor Necrosis Factor α Primes Cerebral Endothelial Cells for Erythropoietin-Induced Angiogenesis

Spi-1/PU.1 but not Fli-1 inhibits erythroid-specific alternative splicing of 4.1R pre-mRNA in murine erythroleukemia cells

Transmembrane signaling during erythropoietin‐ and dimethylsulfoxide‐induced erythroid cell differentiation

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