Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hormones play a role in the regulation of gene expression by inducing changes in enzyme patterns in target cells mediated by the synthesis of specific RNA molecules. Erythropoiesis has been used as a system for studying the molecular mechanism of regulation of gene action by means of two hormones: erythropoietin and testosterone. Experiments designed to correlate the biochemical action of both hormones on rat marrow cells are herein reported. Both factors seems to act at different biochemical and citological levels. Erythropoietin triggers the erythropoietic process acting on the erythropoietin sensitive cells (ESC), in which the hormone induces the synthesis of a high molecular weight RNA, which is the precursor of a functional 9 S messenger RNA. Testosterone seems to act on polychromatophilic erythroblasts, in which the synthesis of ribosomal RNA or its precursor is stimulated. The steroid enhances the nuclear ribonuclease activity, which could represent a control mechanism for the processing (maturation) of high molecular weight RNAs. The incorporation of 3H-GTP and 3H-UTP into RNA by isolated rat bone marrow nuclei is stimulated by erythropoietin and testosterone. Using alpha-amanitine and different ionic strength conditions it was found that erythropoietin enhances preferentially RNA polymerase II activity while testosterone increases RNA polymerase I activity. It is postulated that erythropoietin and testosterone act synergically to create the biochemical machinery for hemoglobin synthesis, the macromolecule that characterizes the erythropoietic process.
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PMID:Hormonal control of gene expression: differential activation of rat bone marrow RNA polymerases by erythropoietin and testosterone. 9 87

Friend murine leukemia virus induces splenic enlargement and an increase in RNA polymerase activity of spleen nuclei. Actinomycin D, administered at 60 mug/kg body weight/day prevents the development os splenomegaly and the elevation of polymerase activity following infection, but it has only a slight effect on the production of virus in spleen tissue. Thus, the alteration of RNA synthesis is not a result of virus proliferation, but instead may be a manifestation of leukemic erythropoiesis. Normal erythropoiesis, stimulated by erythropoietin administration, produces a similar but transient increase in RNA polymerase activity in spleen nuclei. Erythropoietin administered before, but not after, Friend virus infection results in an enhancement of RNA polymerase activity, as measured 9 days after inoculation. This effect is most simply explained by assuming that there is a common target cell pool for both erythropoietin and Friend virus, and that this pool becomes refractory to the influence of the hormone as a result of the leukemic process.
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PMID:Role of cellular RNA polymerases in virus-induced leukemogenesis. 114 21

Globin gene switching in sheep and goats has been used as a model system for examining gene expression in differentiating red blood cells. Sheep and goats switch from the synthesis of hemoglobin A to hemoglobin C in response to erythropoietin. The regulatory mechanism producing this switch in hemoglobin types could occur at the cellular, nuclear, or cytoplasmic level. Evidence is presented which suggests that regulation is occurring, in fact, at the nuclear level. Sheep and goat erythroid colonies have been grown in plasma clot culture in order to study the synthesis of individual globin chains. Erythropoietin is required for colony formation. The switch from hemoglobin A to hemoglobin C synthesis requires not only colony formation but also a higher concentration of erythropoietin than is required just for the production of colonies. A cell-free transcriptional system using bone marrow chromatin and mammalian DNA-dependent RNA polymerase has been developed in order to examine the nuclear control mechanisms in more detail.
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PMID:Activation and inactivation of genes determining hemoglobin types.20s. 116 4

The spleen of the ex-hypoxic polycythemic mouse was employed to study the effect of erythropoietin on nuclear RNA polymerase activity. On the basis of ionic strength requirements and sensitivity to the fungal toxin alpha-amanitin, two major forms (I and II) of nuclear RNA polymerase were identified. Within 0.5 h after administration of erythropoietin, at a time when no morphologically identifiable erythroblasts were present in the spleen, there was an increase in the activity of polymerase II. By 2 h, polymerase II activity had declined to control levels. At 3 h, polymerase I activity began to increase, rising to a peak, 88% above control levels, by 12 h. During this period, early erythroblasts began to appear in the spleen. At 12 h, a second increase of similar magnitude occurred in polymerase II activity. Polymerase I activity fell to control levels by 18 h while polymerase II declined more slowly. These data indicate that stimulation of transcription is an early effect of erythropoietin. Multiple forms of RNA polymerase are involved and activation of these is sequential. Nuclear RNA polymerase activity is maximal during the period of early erythroblast proliferation and declines as these cells mature.
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PMID:Sequential activation of splenic nuclear RNA polymerases by erythropoietin. 124 99

Transplantable erythroblastic leukemia was induced by 300-rad irradiation of C3H mice. Conditions for in vitro growth of the leukemic cells were studied. None of interleukin-3, granulocyte/macrophage colony-stimulating factor and erythropoietin could support the growth of the cells in vitro. In contrast, the leukemic cells grew into a stroma-dependent cell line, ELM-D, in close contact with the stromal cell layer of 900-rad-irradiated long-term bone marrow culture. A stroma-independent cell line, termed ELM-I-1, was further established from the non-adherent population in the co-culture of the leukemic cells, ELM-D, with stromal cells. Reverse transcriptase activity was not detectable in ELM-D or ELM-I-1 cells. Studies on binding and cross-linking of 125I-erythropoietin showed that ELM-I-1 cells had erythropoietin receptors, and two major radiolabeled protein products with molecular weights of 120 kDa and 140 kDa were detected on sodium dodecyl sulfate/polyacrylamide gel electrophoresis under reducing conditions.
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PMID:Stromal cell-dependent growth of leukemic cells from murine erythroblastic leukemia. 246 Apr 23

The cytodifferentiation of stem cells to mature cells in bone marrow is an appropiate system to study biochemical aspects of hormonal action. We have used this system to analyze the way how erythropoietin and testosterone regulate erythropoiesis at the molecular level. Experiments designed to correlate the biochemical action of both hormones and to determine their differential action on rat bone marrow nuclei DNA-dependent RNA polymerases are reported. The effect of both hormones on the synthesis of RNA by isolated nuclei derived from normal rats was studied. Erythropoietin enhances the activity of RNA polymerase type II while testosterone stimulates polymerase type I activity. Gel-electrophoresis analysis of nuclear RNA shows that erythropoietin enhances the synthesis of RNA species with sedimentation coefficients of 30S, 22S, 15S, and 9S. Testosterone stimulates the synthesis of the 28 and 18S RNA as well as 4S RNA. A model is postulated to explain the action of erythropoietin and testosterone on RNA synthesis by isolated rat bone marrow nuclei.
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PMID:Hormonal control of RNA polymerases in rat bone marrow nuclei. The action of erythropoietin and testosterone. 725 8

Introduction of genes for cytokine receptors into hematopoietic stem/progenitor cells (HSC/HPC) may be of clinical use in the future. We recently reported that retroviral-mediated transduction of either the human erythropoietin receptor (hEpoR) or interleukin-9 receptor (hIL-9R) genes into highly purified HSC/HPC from cord blood (CB) resulted in increased numbers of detectable cytokine-responsive erythroid progenitors (burst-forming units-erythroid [BFU-E]). In the present study, we evaluated if this increase could be further enhanced by cotransducing both these genes into single isolated HSC/HPC. Single CD34++CD33-or low-expressing cells from CB were transduced with viral supernatant containing the hEpoR or hIL-9R genes or cotransduced with both genes. In the presence of Steel factor (SLF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo), and IL-9, the numbers of erythroid colonies formed were significantly increased after transduction of cells with either the hIL-9R or hEpoR gene compared to mock-transduced cells. This increase was significantly enhanced in cells cotransduced with both genes compared with either gene alone. Integration and expression of both genes was confirmed by polymerase chain reaction (PCR) and reverse-transcriptase (RT)-PCR analysis, respectively. The data demonstrate that myeloid progenitors can be transduced at the single-cell level with both hEpoR and hIL-9R genes with resultant enhanced proliferation of these progenitors in the erythroid lineage by combinations of cytokines including Epo and IL-9.
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PMID:Influence of retroviral-mediated gene transduction of both the recombinant human erythropoietin receptor and interleukin-9 receptor genes into single CD34++CD33-or low cord blood cells on cytokine-stimulated erythroid colony formation. 864 64

Nontransformed stromal colony-derived cell lines (CDCLs) consist of a pure stromal cell population that differentiates following a vascular smooth muscle cell repertoire, and whose in vivo counterpart is that of myoid cells found in adult and fetal human bone marrow cords. We studied the cytokine expression by reverse-transcriptase polymerase chain reaction (RT-PCR) from pooled fast-growing clones from 10 different bone marrow samples. RT-PCR indicated that 30 cytokines (out of 42 studied) were expressed by CDCLs (20 after medium renewal and hydrocortisone renewal, three after addition of interleukin I beta (IL-1 beta) and seven in only part of the CDCL layers examined). The cytokines expressed comprised mediators known to be involved in the maintenance of early and late hematopoiesis (IL-1 alpha and IL-beta, IL-6, IL-7, IL-8, IL-11 and IL-13; colony-stimulating factors, thrombopoietin, erythropoietin, stem cell factor, fit 3-ligand, hepatocyte cell growth factor, tumor necrosis factor alpha, leukemia inhibitory factor, transforming growth factors beta 1 and beta 3; and macrophage inflammatory protein 1 alpha), angiogenic factors (fibroblast growth factors 1 and 2, vascular endothelial growth factor) and mediators whose usual target (and source) is the connective tissue-forming cells (platelet-derived growth factor A, epidermal growth factor, transforming growth factors alpha and beta 2, oncostatin M and insulin-like growth factor 1), or neuronal cells (nerve growth factor). The cytokines not expressed were lymphokines (IL-2, IL-3, IL-4, IL-5, IL-9, IL-10, and IL-12 and interferon gamma) or mediators synthesized by macrophages (inhibin, activin, platelet-derived growth factor B, and IL-1 receptor antagonist). This study complements the description of the phenotype of the myoid cells, confirming that these cells are the marrow connective tissue-forming cells; moreover, this work suggests that stromal control of hematopoiesis is multifactorial and that myoid cells are involved in the control of marrow angiogenesis and innervation.
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PMID:The broad spectrum of cytokine gene expression by myoid cells from the human marrow microenvironment. 909 Jul 90

Transgenic mice and rabbits were generated using a chimeric gene comprising the human erythropoietin (hEPO) cDNA under the 5' and 3' regulatory sequences of the rabbit whey acidic protein gene. Transgenic mice expressed hEPO at levels of 0.01 mg/l in the milk of lactating females showing that the genetic construct was functional. Reverse transcriptase polymerase chain reaction with RNA from various tissues showed that this transgene was expressed mainly in the ovary and mammary gland. In rabbits, we demonstrated the germ line transmission of the transgene. The hEPO was obtained in the milk of lactating females at levels of up to 0.0003 mg/l. Although the expression levels were low, biologically active hEPO was obtained in the milk of transgenic rabbits without any apparent detrimental effect for the animals. In vitro, the specific activity of the rabbit-derived hEPO was higher than that reported for the natural hEPO, thus suggesting differences in the glycosylation pattern in at least part of the molecules secreted by the mammary gland of transgenic rabbits.
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PMID:Expression of active human erythropoietin in the mammary gland of lactating transgenic mice and rabbits. 925 44

In order to elucidate the components of the oxygen sensory complex in HepG2 cells which regulates the production of erythropoietin, we have microinjected recombinant variants of the human small GTP-binding protein hRac1 and measured their effects on the production of reactive oxygen species (ROS) by the dihydrorhodamine-123 technique. The dominant-negative mutant hRac1(T17N) inhibits the NADH-stimulated production of ROS in HepG2 cells, whereas the constitutively activated hRac1(G12V) leads to an increase in intracellular ROS concentration. Reverse transcriptase PCR analysis showed that the hRac1, but not the hRac2, gene is expressed in HepG2 cells. These results demonstrate that hRac1, and not hRac2, is involved in the regulation of ROS production in HepG2 cells and suggest that hRac1 specifically functions in the non-phagocytic NAD(P)H oxidase complex.
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PMID:Rac1, and not Rac2, is involved in the regulation of the intracellular hydrogen peroxide level in HepG2 cells. 957 45


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