Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

GATA-1, a transcription factor of the 'zinc-finger' family, is required for the development of mature erythroid cells and is also highly expressed in the megakaryocytic and mast cell lineages. The helix-loop-helix gene SCL (or TAL) is expressed in the same three hematopoietic lineages as GATA-1. To explore the role of GATA-1 and SCL in hematopoietic differentiation, we introduced a new expression vector bearing each gene into the early myeloid cell line 416B, which could originally differentiate in vivo along the megakaryocytic and granulocytic lineages. Enforced expression of SCL at high levels did not provoke differentiation, but GATA-1 induced the appearance of megakaryocytes as assessed by morphology, the presence of acetylcholinesterase and a polyploid DNA content. Although GATA-1 is thought to stimulate its own transcription in erythrocytes, expression of the endogenous gene was not increased in the megakaryocytic lines; hence GATA-1 may not be autoregulatory in this lineage. Megakaryocytic differentiation was accompanied by a marked decrease in the myeloid surface marker Mac-1. The absence of mast cell or erythroid differentiation suggests that GATA-1 may not be sufficient to provoke maturation along these lineages or that these pathways are impeded in 416B cells. These results demonstrate that a member of the GATA gene family can act as an important regulator of megakaryocytic differentiation.
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PMID:GATA-1 but not SCL induces megakaryocytic differentiation in an early myeloid line. 138 17

Features of true acetylcholinesterase (AChE) regulation during growth and differentiation of Friend murine erythroleukemia cells (MELC) have been investigated with respect to other erythroid and nonerythroid murine elements. Enzyme levels of uninduced MELC were in between the very low AChE contents of erythroid cells and the huge amounts of activity exhibited by megakaryocytes and platelets. After MELC commitment to terminal division, the enzyme-specific activity increased largely, approaching values that were much closer to those of thrombocytic than of normal erythroid elements. The bulk of AChE activity in MELC, megakaryocytes, and platelets was found to be located in the cytosol as a free-soluble form. Moreover, during incubation, MELC actively released large amounts of AChE into the medium, like it occurs in murine thrombocytes. Conversely, the enzyme of the erythroid elements was mainly associated with the membranes and was not released extracellularly. Experiments with inducers showed that changes in AChE-specific activity of MELC correlated directly with the arrest of cell proliferation rather than with the activation of differentiated erythroid functions. The inverse relationship existing between MELC growth rates and AChE levels was further supported by the relative enzyme activities of the slow- and fast-growing subclones. We conclude that uninduced MELC potentially share properties of both the erythroid and megakaryoblastic phenotype. The latter might be revealed by typical regulation of AChE activity according to a thrombocytic-like program activated upon MELC commitment to terminal division. Eventually, the inhibition of MELC growth by exogenous pure bovine AChE suggested that the secreted murine enzyme might serve as a potential negative signal of cellular replication.
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PMID:Acetylcholinesterase in murine erythroleukemia (Friend) cells: evidence for megakaryocyte-like expression and potential growth-regulatory role of enzyme activity. 158 35

Acetylcholinesterase (AChE; EC 3.1.1.7) is present in both primitive and mature erythroid cells, and a role has been suggested for the enzyme in regulation of differentiation in the human erythron. AChE is also a major enzyme in the central nervous system; alteration of its activity has been proposed as a therapeutic strategy in Alzheimer disease. We recently treated 18 Alzheimer disease patients with metrifonate, a long-acting AChE inhibitor, over periods up to 7 months, with resulting erythrocyte AChE inhibition as high as 82 per cent of baseline values. Despite chronic reduction of enzyme activity, no significant alterations were noted in erythrocyte, leukocyte or platelet characteristics or numbers that would suggest a deleterious effect of AChE inhibition on normal differentiation. Thus, any modification of developmental pathways appears to be compensated by other regulatory mechanisms in the intact organism.
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PMID:Stability of peripheral hematological parameters after chronic acetylcholinesterase inhibition in man. 185 89

The Belgrade laboratory (b/b) rat has a hereditary hypochromic microcytic anemia because of defective transmembrane iron transport into erythroblasts. The present study was prompted by our previous work in which we showed that the b/b rat has hypomegakaryocytic thrombocytopenia associated with increased megakaryocyte size. To define the basic mechanism underlying this abnormality in the b/b rat we have studied both megakaryocytopoiesis and granulopoiesis in anemic b/b rats, chronically transfused b/b rats, iron-treated b/b rats, and controls. We have found decreased concentrations of megakaryocyte and granulocyte progenitors in the marrow of b/b rats. Full correction of the severe anemia by chronic transfusion resulted in normalization of megakaryocyte progenitors, small acetylcholinesterase positive cells, megakaryocyte size, and platelet counts, along with granulocyte progenitors. In contrast, the partial correction of anemia obtained by iron treatment resulted in improvement, but not normalization, of these parameters. These findings indicate that abnormal megakaryocytopoiesis in the b/b rat can be best interpreted as a consequence of hypoxia because of the severe anemia. Because we have recently shown that the number of erythroid progenitors in b/b rats is also low, we propose that abnormal megakaryocytopoiesis in this animal is a reflection of an acquired stem cell disorder induced by the prolonged hypoxia resulting from the severe anemia.
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PMID:Abnormal megakaryocytopoiesis in the Belgrade laboratory rat. 199 Nov 62

We have isolated cDNA clones encoding acetylcholinesterase from mouse muscle and brain. The polymerase chain reaction was used to amplify cDNA clones from C2 myotubes encoding the entire open reading frame and large segments of the 5' and 3' untranslated regions. The muscle cDNA clones were used to isolate clones from a brain library encoding the same mRNA species. The mouse clones encode a catalytic subunit containing a C-terminal sequence similar to that of the hydrophilic species of Torpedo. The mouse acetylcholinesterase sequence shares approximately 88% and 61% amino acid identity with bovine and Torpedo acetylcholinesterases, respectively, but only 52% identity with mouse butyrylcholinesterase, the sequence of which we have also deduced by molecular cloning. Northern blot and RNAase protection analyses indicate that the cDNA clones were derived from the acetylcholinesterase transcript that predominates in most expressing tissues. In contrast, erythroid cells are enriched in an mRNA species whose sequence diverges from that of the cDNA in the region encoding the C-terminus of the enzyme.
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PMID:Molecular cloning of mouse acetylcholinesterase: tissue distribution of alternatively spliced mRNA species. 240 Jun 5

Acetylcholinesterase (AChE) is an integral erythrocyte membrane protein. A role for the enzyme in the developing human erythron is being explored. Assays of AchE by the standard Ellman technique overestimate the amount of enzyme by failing to account for the contribution of hemoglobin to the optical density of the reaction mixture. Furthermore, reliance on substrate selection alone for specificity is unsatisfactory. Incorporation of inhibitors of "true" AchE and of pseudocholinesterase confer greater ability to distinguish one enzyme from the other. In our experience, the inhibitor constant (Kl) for edrophonium, which is highly specific for AChE, is approximately 5 x 10(-5) M against adult human erythrocytes that contain significantly more total cholinesterase activity than do erythrocytes from umbilical cord blood. This consists of both "true" and "pseudo" enzyme, the former predominating and accounting for 0.75-1.65 (mean 1.02, median 0.87) femtomoles of substrate hydrolysed per min per cell in adult blood, with values of 0.15-1.04 (mean 0.71, median 0.73) obtained on cord blood. Moreover, the enzyme activity in neonatal erythrocytes has a rather different inhibitor profile from that of adult cells. AChE was also demonstrated in fresh (ALL) and cultured (K562 and HL60) human leukemic cells, as well as in primitive granulocyte-macrophage and erythroid cells cloned from normal human bone marrow. In the erythroid colonies the enzyme activity was 0-3.76 (mean 1.20, median 0.76) femtomoles per min per cell, apparently the first successful measurement of AChE in such cells.
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PMID:Acetylcholinesterase in the human erythron. II. Biochemical assay. 316 38

A factor that stimulates the incorporation of 75Selenomethionine into the newly formed platelets of recipient mice (thrombopoietin, TPO) has been partially purified from the plasma of thrombocytopenic patients. The activity was precipitated at 60-80% ammonium sulfate saturation and further purified with hydrophobic interaction chromatography. Thrombopoietin was retained by concanavalin-A-Sepharose. Using HPLC size-exclusion chromatography, an approximate molecular weight of 40,000 dalton was calculated. The overall purification factor was about 2,100-fold. TPO was stable in a pH range from 5 to 9 and was heat-sensitive, and the biological activity was destroyed by trypsin treatment and by dithiothreitol. The partially purified molecule did not stimulate the proliferation of megakaryocyte progenitors in vitro and had no effect on the growth of erythroid or granulocyte-macrophage colonies; when administered in-vivo, TPO significantly affected the mean platelet volume and increased the number of small acetylcholinesterase cells in the bone marrow. TPO appears to be specific for the megakaryocytic lineage and active on the postmitotic compartment of megakaryocytes.
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PMID:Partial purification and biochemical characterization of human plasma thrombopoietin. 336 51

The successful demonstration and localisation of acetylcholinesterase (AChE), in cells by a cytochemical technique requires maximal expression of enzyme activity, minimal loss of AChE and precise, quantitative generation of reaction product at the actual site of the protein in vivo. These requirements are addressed in a standard technique that has been modified to avoid or optimise fixation and to exhibit enzyme activity under close-to-physiological conditions of osmolality, pH, and temperature. With these refinements and with the use of a variety of substrates and enzyme inhibitors of different specificities, true AChE was demonstrable on the membrane of erythrocytes and in the nucleus and cytoplasm of erythroblasts in bone marrow and of the constituent cells of erythroid clones in vitro. The activity in erythrocytes from umbilical cord blood was less than that in corresponding cells from the peripheral circulation of adults. AChE was observed also in human megakaryocytes and in leucocytes at all levels of differentiation, including the components of granulocyte-macrophage clones. Pseudocholinesterase was detected likewise across the spectrum of erythroid (and leucocyte) ontogeny, suggesting that these enzymes may exercise an important function in hematopoiesis.
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PMID:Acetylcholinesterase in the human erythron. I. Cytochemistry. 341 73

The alteration of acetylcholinesterase (ACHE) activity, a marker enzyme of erythroid differentiation, was studied during the hemin-induced erythroid differentiation of K562 human leukemia cells in suspension culture. The kinetics of postinduction differentiation was followed by determining the hemoglobin (Hb) content and the ACHE activity of cells. Embryonic hemoglobins as well as small quantities of fetal Hb (HbF) were synthetized by stimulated cells. The peaks of ACHE activity preceded the highest level of Hb content and, following induction, reached their pinnacles at 72 and 120 hours, respectively. These data indicate that ACHE activity is an earlier and more sensitive marker for hemin-induced erythroid differentiation of K562 cells than is elevated Hb content. Electrophoretic mobility of ACHE from hemin-treated cells proved to be the fetal type, but after incubation with neuraminidase, the rate of migration decreased to the level of the adult type enzyme.
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PMID:Characterization of "fetal-type" acetylcholinesterase in hemin-treated K562 cell culture. 347 1

Two erythroid markers, acetylcholinesterase and hemoglobin, can be reversibly induced in the K-562 cell line after sodium butyrate treatment. In the present paper we show that 1-beta-D-arabinofuranosylcytosine (ara-C), induces the coordinate, irreversible expression of these two erythroid markers. This induction occurs at an ara-C concentration (0.05 mM) that results in K-562 cytostasis and is accompanied by deep morphological changes of cells. The differentiated phenotype is independent of the K-562 cell clone used [K-562, K-562 (S), K-562 (S)P] and is associated with the loss of cell renewal capacity. Continuous presence of the inducer is not necessary to achieve terminal differentiation. In contrast to what is seen for other inducers (sodium butyrate and hemin), one of the early effects of ara-C treatment is the marked decrease of c-myc mRNA expression after the first 4 hours of induction, whereas N-ras and histone 4 expression remain constant during the first 48 h. Our results suggest that ara-C treatment can irreversibly activate the erythroid differentiative program of K-562 cells.
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PMID:Terminal erythroid differentiation in the K-562 cell line by 1-beta-D-arabinofuranosylcytosine: accompaniment by c-myc messenger RNA decrease. 353 78


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