Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of Friend erythroleukemia cells with several different chemical agents causes an early decrease in the 86Rb+ influx mediated by Na+/K+ adenosine triphosphatase (ATPase). These agents, which induce Friend cells to differentiate, include dimethylsulfoxide (DMSO), ouabain, hypoxanthine, and actinomycin D. The magnitude of the early decrease in 86Rb+ influx correlates with the proportion of cells in cultures of inducible Friend cell clones which later go on to synthesize hemoglobin. Compounds which do not incude differentiation in these cells, such as xanthine, exogenous hematin, and erythropoietin, do not cause a change in 86Rb+ influx. A change in the intracellular K+ ion concentration does not occur during induction by DMSO because, although there is a decrease in K+ content per cell soon after induction, there is a parallel decrease in cell volume. These results and previous observations from this laboratory are discussed in terms of the posible involvement of the Na+/K+ ATPase in Friend cell differentiation.
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PMID:The program of Friend cell erythroid differentiation: early changes in Na+/K+ ATPase function. 21 40

Experimental infection of hamsters with Leishmania donovani caused visceral leishmaniasis in which hematological changes occurred. The infected hamsters were anemic and reticulocyte counts were high. No significant change in the serum erythropoietin level was noted. Red cell membrane Na(+)-K(+)-ATPase and acetylcholinesterase activities increased. Osmotic fragility of the erythrocytes from infected animals increased. The level of 2,3-diphosphoglycerate of the red cells increased with the degree of anemia.
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PMID:Anemia in experimental visceral leishmaniasis in hamsters. 131 Jul 31

The effect of erythropoietin (Ep), a glycoprotein hormone, has been studied on lipid peroxidation induced by Cu2+ and ascorbate in vitro, Mg2+ ATPase activity and spectrin of RBC membrane. Our present investigation reveals that Cu2+ and ascorbic acid increases lipid peroxidation of RBC membrane significantly. It has further been observed that under the same experimental condition spectrin, a major cytoskeleton membrane protein, and Mg(2+)-ATPase activity of RBC membrane decrease significantly. However, exogenous administration of Ep completely restores lipid peroxidation and Mg(2+)-ATPase activity and partially recovers spectrin of RBC membrane.
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PMID:Effect of Cu(2+)-ascorbic acid on lipid peroxidation, Mg(2+)-ATPase activity and spectrin of RBC membrane and reversal by erythropoietin. 133 13

Thyroid hormones modulate energy metabolism and importantly influence growth and development. These effects are independently mediated. Thyroid calorigenesis is influenced predominantly via nuclear receptor mediated synthesis of mitochondrial respiratory assemblies and cell membrane sodium potassium ATPase. Accumulating evidence suggests that many of the thyroid hormone effects on development are mediated via growth factors, including somatomedins (SM), erythropoietin (EP), nerve growth factor (NGF) and epidermal growth factor (EGF). Thyroid hormone binding to nuclear receptors is known to stimulate growth hormone (GH) synthesis, and thyroid hormones probably potentiate GH stimulation of SM production as well as the anabolic effects of SM. The production of EP, NGF and EGF also are thyroid hormone responsive, and it seems likely that these growth factors mediate the thyroid hormone effects on erythrocyte production, autonomic and perhaps central nervous system maturation, and epidermal development, respectively.
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PMID:The thyroid hormone effects on growth and development may be mediated by growth factors. 621 63

Ouabain enhances the number of clonally derived erythroid stem cell colonies (CFU-e and BFU-e) from normal murine bone marrow. Ouabain is known to inhibit lymphocyte proliferation by blocking the Na+/K+ pump. To further explore these Na+/K+ ATPase-associated interrelationships, valinomycin, an inhibitor of Na+/K+ ATPase was employed. The addition of valinomycin (10(-11) to 10(-15) M) in the presence of ouabain and erythropoietin (Ep) did not alter the erythroid colony-forming stimulation which was characteristic of cultures in which only ouabain (10(-15) M) and Ep were added. Valinomycin did effectively block both CFU-e and BFU-e formation when it was added in the range of 10(-3) to 10(-9) M. The mechanism of this valinomycin-induced inhibition and ouabain stimulation is discussed.
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PMID:Effects of ouabain and valinomycin on in vitro erythroid colony formation (CFU-e and BFU-e). 714 Oct 69

Erythropoietin is considered unique among the hematopoietic growth factor with a specific action on the differentiation and proliferation of erythroid progenitor cells. We have observed a dose-dependent modulatory action of human recombinant erythropoietin (rHuEpo) stimulated the rate of cell growth but at higher ones (3-10 U/ml) inhibited it. The mitogenic action of the hormone is correlated with cardiac membrane Na(+)-K(+)-ATPase activity since concentrations of rHuEpo that increased cell growth stimulated paranitrophenilphosphatase (pNPPase) activity, while those concentrations that inhibit the enzyme markedly bloqued its mitogenic action. Moreover, ouabain (10(-5) M), concentration that inhibits Na(+)-K(+)-ATPase activity, blunted the stimulatory action of rHuEpo on cell proliferation. We also demonstrated that rHuEpo while activated the cardiac membrane Na(+)-K(+)-ATPase was able to alter the contractile action of ouabain on isolated neonatal rat atria. Indeed rHuEpo (1 U/ml) enhanced the non toxic action of the cardiac glycoside attenuating and delaying the onset of the toxic effect of the drug. These results show that rHuEpo has a non hematopoietic cardiac effect, associated with the cardiac Na(+)-K(+)-ATPase activity, that regulates the myocytes growth and the biological action of cardiac glycosides on isolated rat myocardium.
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PMID:Myocardial mitogenic effect of erythropoietin through the activation of Na(+)-K(+)-ATPase activity. 764 Mar 98

Bone marrow stromal cells serve hematopoietic microenvironments where different blood cells are controlled in their growth and differentiation. To characterize functions of stromal cells, 33 bone marrow stromal cells including preadipocytes, endothelial cells, and fibroblasts were established from transgenic mice harboring temperature-sensitive SV40 T-antigen gene and their selective stimulatory abilities to support large colony formation of lineage-specific hematopoietic progenitor cells (erythroid, monocyte/macrophage, granulocyte, and monocyte-granulocyte) were examined. Among established stromal cells, 27 clones showed erythropoietic stimulatory activity in the presence of erythropoietin. On myeloid progenitors, the stromal cells showed lineage-restricted stimulatory activity and a reciprocal relationship was observed between granulocyte formation and macrophage formation, but these activities were not dependent on the amount of produced colony-stimulating factors (CSFs). Our present study with many stromal cells established from bone marrow indicated that each stromal cell in the bone marrow may provide the preferable microenvironment for a rapid expansion of the lineage-restricted progenitor cells in combination with CSFs.
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PMID:Bone marrow stromal cells selectively stimulate the rapid expansion of lineage-restricted myeloid progenitors. 779 Mar 97

Proteins transiting the secretory pathway are posttranslationally modified by addition of oligosaccharides to asparagine N-linked and serine and threonine O-linked residues. The effects of divalent cation depletion on oligosaccharide processing of erythropoietin (EPO) and macrophage colony stimulating factor (M-CSF) were studied in Chinese hamster ovary cells. Treatment with A23187 did not inhibit M-CSF or EPO secretion but did inhibit addition of complex N-linked and O-linked oligosaccharides to both molecules. Similar results were obtained by treatment with thapsigargin, a potent inhibitor of the Ca(2+)-activated microsomal ATPase, indicating that the effect was due to depletion of divalent cations within the secretory pathway. Whereas addition of extracellular calcium chloride did not reverse the inhibition in complex N-linked and O-linked glycosylation, addition of manganese chloride partially reversed both defects. These results are consistent with a specific manganese requirement within the secretory pathway for the processing of complex N-linked oligosaccharides and the addition of O-linked oligosaccharides. Since there are no known specific inhibitors of O-linked glycosylation, the use of ionophores should significantly facilitate studies on the requirement and role of O-linked oligosaccharides in protein structure and function.
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PMID:Depletion of manganese within the secretory pathway inhibits O-linked glycosylation in mammalian cells. 806 Sep 88

We have developed an intermediate method toward the complete carbohydrate analysis of proteins, which should be universally applicable to all proteins and independent of sample matrix. Using only Coomassie Blue-stained proteins which have been electroblotted onto polyvinylidene fluoride membranes, we report a strategy for: (i) determining unequivocally whether a protein is glycosylated; (ii) obtaining a complete monosaccharide composition; (iii) oligosaccharide mapping which separates most forms according to size, charge and isomerity; and (iv) sequentially releasing and analyzing specific classes of oligosaccharides with endoglycosidases. The method was shown to be applicable to a variety of well characterized soluble glycoproteins and to the membrane-bound protein, the gastric H+, K(+)-ATPase. The monosaccharide composition of the H+,K(+)-ATPase revealed the absence of N-acetylneuraminic or N-glycolylneuraminic acids and a monosaccharide composition which indicated O-linked sugar chains. Oligomannosidic/hybrid and biantennary oligosaccharides were sequentially released and analyzed from one electroblotted band of recombinant tissue plasminogen activator using endo-beta-N-acetylglucosaminidase H and endo-beta-N-acetylglucosaminidase F2, respectively. Sialylated polylactosamine structures were identified and quantified by analyzing high performance liquid chromatography profiles of oligosaccharides first released by peptide-N4-(N-acetyl-beta-D-glucosaminyl)asparagine amidase and then treated with endo-beta-galactosidase, using a single, stained band of recombinant erythropoietin. This recombinant erythropoietin was found to contain eight times more tetrasialylated oligosaccharides than previously reported (Sasaki, H., Bothner, B., Dell, A., and Fukuda, M. (1987) J. Biol. Chem. 262, 12059-12076); 47% of released oligosaccharides were identified as polylactosamine structures.
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PMID:Monosaccharide and oligosaccharide analysis of proteins transferred to polyvinylidene fluoride membranes after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 844 88

The results of the studies reported here demonstrate the cardiac non-haematopoietic effect of erythropoietin, providing a new physiological function of the hormone. We demonstrate that myocardium from rat with chronic renal failure (CRF) showed an abnormal response to ouabain associated with an inhibition of cardiac Na+/K+/ATPase activity and with a decrease in the high affinity 3H-ouabain binding sites. The extent to which both actions were improved with the recombinant human erythropoietin (rHuEpo) treatment suggests that the lack of the hormone is responsible for this phenomenon. The fact is that neither contractile nor enzymatic action of rHuEpo was accompanied with the improvement of the functional renal and haematologic parameters, indicating a primary effect on myocardial contractile function of rHuEpo, independent of the anaemic and uraemic state of the animal. The reason why erythropoietin is able to modulate directly the cardiac Na+/K+ pump makes it possible to conclude that the lack of erythropoietin in CRF may be at least in part responsible for the inhibition of cardiac enzymes, altering the contractile behaviour of the heart.
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PMID:Erythropoietin modified the cardiac action of ouabain in chronically anaemic-uraemic rats. 856 53


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