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:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight 5'-(steroid-21-phosphoryl)-9-(beta-D-arabinofuranosyl)-adenines (IV-XI) have been prepared and evaluated against L1210 lymphoid leukemia in culture. These include the 9-(beta-D-arabinofuranosyl)adenine conjugates of hydrocortisone (IV), cortisone (V), corticosterone (VI), cortexolone (VII), 11-deoxycorticosterone (VIII), prednisolone (IX), prednisone (X), and dexamethasone (XI). Conjugates IV, IX, X, and XI inhibited the in vitro growth of L1210 lymphoid leukemia cells by 50% (ED50) at a concentration of 2.3-7.8 microM, while 9-(beta-D-arabinofuranosyl)adenine (vidarabine, I) and its 5'-monophosphate (II) each showed ED50 value of 30 microM. All of the conjugates were enzymatically hydrolyzed to the corresponding steroid and II, the latter undergoing further hydrolysis to I, by phosphodiesterase I, 5'-nucleotidase, and acid phosphatase. However, these conjugates were resistant to hydrolysis by alkaline phosphatase and adenosine deaminase.
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PMID:Nucleoside conjugates V: Synthesis and biological activity of 9-(beta-D-arabinofuranosyl)adenine conjugates of corticosteroids. 670 3

It has been shown that low concentrations of E. coli lipopolysaccharides (LPS) greatly and selectively stimulate phagocytosis and related functions in mouse bone marrow-derived macrophages. Culture in the presence of 50 ng/ml LPS induced on average a 10-fold enhancement of phagocytosis of IgG-coated sheep erythrocytes. Activation was in two stages--a small increase observed during the first 8 to 12 hr, and the major increase noted between 16 and 24 hr. Phagocytic activity remained at the maximal level for 24 hr and then declined progressively. Stimulation by LPS was dose-dependent; significant effects could be observed at 0.8 ng/ml and the maximum was reached at 10 ng/ml. LPS-treated cells also showed a markedly increased tendency to form colonies. All these effects could be prevented by the addition of 100 ng/ml polymyxin B together with LPS, indicating that the active principle is lipid A. The LPS-dependent increase in phagocytic activity is probably mediated by increased Fc receptor capacity because both parameters were influenced in parallel by the stimulus. Phagocytosis-related events, such as enhanced hexose monophosphate shunt activity, H2O2 formation, and nitroblue tetrazolium reduction were also stimulated by LPS. By contrast, pinocytosis was unaffected. Measurements of cell-associated enzyme activities showed that lactate dehydrogenase, acid phosphatase, and cathepsin D were significantly increased. Beta-glucuronidase, beta-galactosidase, alkaline phosphodiesterase, and aminopeptidase were unchanged and NAD nucleosidase was markedly decreased after LPS treatment. 5'-Nucleotidase and glucosamine uptake were undetectable both in control and LPS-stimulated cells. LPS treatment induced a significant increase in cell-associated protein, but did not result in cell proliferation or increased cell loss as shown by the DNA content that remained constant. LPS-induced changes were dependent on de novo protein synthesis; cycloheximide prevented enhancement of phagocytosis, Fc receptor capacity, and colony formation.
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PMID:Stimulation of phagocytosis in bone marrow-derived mouse macrophages by bacterial lipopolysaccharide: correlation with biochemical and functional parameters. 673 51

The present study examines the role of cardiac lysosomal enzymes in the pathogenesis of the cardiomyopathy that develops in genetically diabetic C57BL/KsJ db+/db+ mice. Db+/db+ mice and littermate controls were sacrificed as age-matched pairs between 5-26 weeks of age. C57BL/6J ob/ob mice and littermates served as other controls. The hearts were excised, homogenized, and the following enzymatic activities measured: N-Acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, beta-glucosaminidase, aryl sulphatase, alpha-mannosidase, alpha-glucosidase, beta-galactosidase, beta glucosidase, total p-nitrophenyl phosphatase, acid phosphatase and 5'-phosphodiesterase type IV. There is a progressive decrease in cardiac lysosomal enzyme activities of db+/db+ mice for the period 5-21 weeks of age. All enzyme activity is depressed significantly during the 9-21 week interval with beta-glucuronidase, aryl sulphatase and beta-glucosidase decreased about 40-50%. The decrease in lysosomal enzyme activity can explain the accumulation of large residual bodies and interstitial material in the myocardium of the db+/db+ animals
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PMID:Lysosomal enzymes in experimental diabetic cardiomyopathy. 678 Feb 37

Screening of several fungal cultures resulted in the selection of an isolate of Aspergillus candidus which produced a considerable around of RNa-degrading enzyme in both surface and submerged methods of cultivation. The conditions for the assay of the RNAase were standardized at pH 4.5, 55 degrees C and using 0.25% yeast RNA as substrate. The enzyme was stable at pH 5.2. EDTA was found to activate the enzyme slightly. at temperatures 50-60 degrees C there was considerable loss in enzyme activity which was traced to the presence of a contaminating protease which presumably degraded the RNAase optimally at this temperature. The protease could be preferentially inactivated at or above 75 degrees C. The crude enzyme, in addition to RNAase was found to possess DNAase, nonspecific phosphodiesterase and 3'- and 5'-phosphomonoesterase activities.
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PMID:Standardization of assay procedure and some properties of ribonuclease from Aspergillus candidus. 679 71

Lysosomes form an integral part of the degradative mechanisms of the phagocytic cells. Mice were injected with suramin, a lysosomotrophic drug, to investigate the effects of lysosomal pathology on the cell biology and in situ bactericidal activity of the pulmonary macrophage. Treatment with suramin resulted in marked alterations in the cell biology of the macrophage: (i) increased vacuolization and protein content, (ii) suppressed intracellular phagosome-lysosome fusion, (iii) decreased activity of the lysosomal enzymes beta-glucuronidase and N-acetyl-glucosaminidase, and (iv) enhanced exocytosis of acid phosphatase during phagocytosis. Addition of suramin, in vitro, to cell lysates resulted in a reduction in the catalytic activities of acid phosphatase, beta-glucuronidase, and N-acetyl-glucosaminidase; thereby suggesting that selective interaction, in vivo, between suramin and lysosomes containing beta-glucuronidase and N-acetyl-glucosaminidase may have occurred. Plasma membrane 5'-nucleotide phosphodiesterase activity was increased in macrophages recovered from suramin-treated animals. Although the "resting-state" reduction of nitroblue tetrazolium (NBT) was lower in these macrophages, cells stimulated by a phagocytic challenge demonstrated normal increases in NBT reduction. Phagocytosis, in vitro, and pulmonary bactericidal activity were not altered. These data demonstrate that suramin altered numerous aspects of the phagocyte's lysosomal system. Despite these changes in the cell biology of the pulmonary macrophage, the cell's defense functions were not reduced.
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PMID:Lung macrophage defense responses during suramin-induced lysosomal dysfunction. 683 43

Polymorphonuclear leucocytes were isolated from pig blood relatively free from other cells and were characterised biochemically and morphologically and compared with human PMNLs. The activities of 16 enzymes of porcine and human PMNLs were measured and compared. Alkaline phosphatase, acid phosphatase, phosphodiesterase, gamma-glutamyl transpeptidase, NADH-cytochrome c oxidoreductase, malate dehydrogenase and acetylcholinesterase had higher specific activities in procine than in human cells. Alkaline phosphatase has an 87-fold higher specific activity in porcine than in human cells. beta-glucuronidase, lysozyme, beta-galactosidase, N-acetyl-glucosaminidase, beta-glucosidase, myeloperoxidase and catalase had higher specific activities in human than in porcine cells. beta-glucuronidase and myeloperoxidase showed over a 1000- and a 13-fold higher specific activity, respectively, in human than in porcine cells. Porcine PMNLs are readily available in large numbers and are recommended for studies of phagocytosis, chemotaxis and membrane biochemistry.
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PMID:Biochemical characterisation of porcine polymorphonuclear leucocytes: comparison with human polymorphonuclear leucocytes. 687 22

A Golgi-rich fraction has been isolated from rat ascites hepatoma AH-130 cells. Unlike the usual procedure for isolating Golgi complexes from liver and other tissues, a hypotonic solution including 2 mM CaCl2 was used as the homogenization medium for the ascites hepatoma cells, followed by a combination of differential and discontinuous sucrose gradient centrifugations. Electron microscopic observation revealed that the isolated fraction consisted of cisternae, vesicles and tubular elements which were similar to those structures described previously for the Golgi fraction isolated from rat liver. Galactosyl- and sialyl-transferases were concentrated about 55- and 75-fold, respectively, in this fraction compared with the homogenate, indicating that these enzymes are useful markers for the Golgi complex of rat ascites hepatoma AH-130 cells, as they are for those of other normal tissues. The preparation was virtually free of cytochrome oxidase, but contained minor amounts of acid phosphatase, alkaline phosphatase and phosphodiesterase I activities. Electrophoretic analysis on sodium dodecylsulfate-polyacrylamide gels showed that the hepatoma Golgi membranes were resolved into at least 23 protein bands, which were apparently different from the electrophoretic profile of the plasma membrane isolated from the same hepatoma cells.
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PMID:Isolation and characterization of the Golgi complex from rat ascites hepatoma AH-130 cells. 714 13

Activities of lysosomal hydrolases were measured in the leucocytes of cattle, sheep, goats, horses and pigs. There was high activity of arylsulphatase in leucocytes from cattle, high activities of alpha-fucosidase and beta-glucuronidase in leucocytes from horses and high activity of acid phosphatase in granulocytes from pigs. Within species, arylsulphatase and beta-galactosidase activities were higher in granulocytes than in mononuclear cells, but beta-glucuronidase, phosphodiesterase and alpha-galactosidase activities were higher in mononuclear cells than in granulocytes. Eosinophils of cattle, sheep, goats and horses contained at least 10 times the activity of alpha-mannosidase and arylsulphatase found in neutrophils. For most of the other enzymes studied, there were differences in cattle and goats but not in sheep, horses or pigs between their specific activities in neutrophils and eosinophils.
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PMID:Lysosomal hydrolase activity in leucocytes from cattle, sheep, goats, horses and pigs. 715 6

Plasma membranes were isolated from lactating bovine mammary gland. Two crude membrane fractions; medium/d 1.033 (light membrane) and 1.033/1.053 interfaces (heavy membrane), were obtained by Ficoll density gradient centrifugation of osmotically washed microsomal fraction. Two crude membranes were further purified separately by sucrose density gradient centrifugation. Both light and heavy membranes banded at a sucrose density of 1.14. The purified membranes appeared as heterogeneous smooth membrane vesicles on electron microscopy. The contaminating suborganelles were not detected. The yield of the purified membranes relative to the homogenate was 1.2%. The degree of purity of the membranes was shown by a great increase in the specific activity of 5'-nucleotidase over the homogenate of 20-fold for light membrane and of 16-fold for heavy membrane. The relative activities of Mg2+-ATPase, (Na+ + K+)-ATPase, gamma-glutamyl transpeptidase, phosphodiesterase I, alkaline phosphatase and xanthine oxidase were also high (12-18-times) and nearly 20% of these enzymes was recovered. The activity of marker enzyme for mitochondria, endoplasmic reticulum and Golgi apparatus was very low, while that of acid phosphatase for lysosome was relatively high (5-times). DNA and RNA contents were very low. The major polypeptides rich in other suborganelles were not detected profoundly in the membrane fraction and the polypeptide composition in both light and heavy membranes were similar upon SDS-polyacrylamide gel electorphoresis.
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PMID:Isolation and characterization of plasma membrane from lactating bovine mammary gland. 720 55

Homogenates of the posterior latissimus dorsi muscle, a phasic muscle, were fractionated by a one-step zonal centrifugation technique into four major organelle populations and cytoplasmic constituents. These were: (1) Plasma membrane fragments with a modal equilibrium density of 1.10 and containing 5'-nucleotidase, alkaline phosphodiesterase, p-nitrophenylphosphatase and acid phosphatase (beta-glycerophosphate was used as the substrate). (2) Sarcoplasmic reticular fragments which could be further subdivided into calcium transport vesicles, with a model equilibrium density of 1.16, that exhibited calcium uptake; K+-ATPase; leucyl-bet-naphthylamidase; acid phosphodiesterase; acid phosphatase (using cytidine monophosphate as the substrate); and sarcoplasmic reticular lysosomes, with a model equilibrium density of 1.18, possessing dipeptidyl-aminopeptidase II, cathepsin D, alpha-glucosidase, N-acetyl-beta-glucosaminidase, and NADH oxidase activity. (3) Mitochondria with a modal equilibrium density of 1.21. (4) Catalase-containing vesicles with a modal equilibrium density of 1.22; and cytoplasmic constituents (modal density of 1.25) with phosphorylase, pyruvate kinase, myosin-ATPase, aldolase, and protein and RNA content. The purity of these organelles was equal to or better than previous efforts, with a 30-fold purification achieved for 5'-nucleotidase and alkaline phosphodiesterase. These results lend support to the hypothesis that the sarcoplasmic reticulum of phasic muscle, in addition to its specialized role in excitation-contraction coupling, represents a multifunctional membrane system, and that, similar to the smooth endoplasmic reticulum of other cells, it includes some membrane-bound lysosomal enzymes and NADH oxidase.
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PMID:Isopycnic-zonal centrifugation of plasma membrane, sarcoplasmic reticular fragments, lysosomes, and cytoplasmic proteins from phasic skeletal muscle. 721 87


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