Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In attempting to understand the causes of the hyperglycaemia observed in aging populations and to determine the mechanism(s) for the diminished in vitro insulin release from islets of Langerhans of older rats, the adenylate cyclase-cyclic AMP system was studied in isolated islets from 12 month old and 2 1/2 month old (control) male rats to determine its role in this altered insulin secretion. Islets of Langerhans were isolated by collagenase digestion and then either incubated in the presence of low or high concentrations of glucose for studies of insulin release or were sonicated and assayed for determinations of activities of adenylate cyclase and phosphodiesterase. Insulin release was identical from islets of 12 month old and 2 1/2 month old rats to 2.8 mM D-glucose, while in the presence of 16.7 mM D-glucose, insulin release was decreased by 33% (P less than 0.02) from islets of the older animals. Adenylate cyclase activity was diminished by 60% (P less than 0.005) from the 12 month old rats as compared with islets from the 2 1/2 month old controls, while low Km phosphodiesterase activity was similar in islets from both groups of animals. From these studies it appears that the adenylate cyclase-cyclic AMP system may play a role in the altered insulin release from islets of aging rats.
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PMID:Role of the adenylate cyclase system in altered insulin release from islets of Langerhans of aging rats. 625 70

The presence of phosphodiesterase IV has been demonstrated in the human fetal brain, liver and placenta as early as in the 6th week of intrauterine development. The enzyme activity in each tissue increases with gestation, being maximum at 18-21 wk and then decreases. The Km values of this enzyme for bis-(p-nitrophenyl)-phosphate hydrolysis in the brain, liver and placenta are 2.94 mM, 1.47 mM and 1.66 mM, respectively. Presence of sulfhydryl group in the active center of the placental enzyme has been demonstrated with the help of cationic study. EDTA inhibits the enzyme in all three tissues. Effect of concanavalin A reveals the absence or unexposition of glucose, mannose and N-acetylglucosamine moieties in the active site of the enzyme in each of the three tissues. Maximum enzyme activity has been found to be localized in the soluble supernatant fraction obtained on centrifuging the brain and liver homogenate at 105,000 x g and in 20,000 x g pellet of the placenta.
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PMID:Occurrence of phosphodiesterase IV in the developing human brain, liver and placenta. 628 89

The ability of nonionic detergents to solubilize the membrane-bound enzymes of the brush-border plasma membrane of Hymenolepis diminuta was investigated. Of the detergents tested (Triton X-100, Tween 80, Brij 35, Lubrol PX and WX, W-1, and beta-octyl-D-glucoside), only Triton was an effective solubilizing agent. Optimal solubilization was achieved by incubating an isolated fraction of the brush-border membrane in the presence of 1% Triton X-100 for 60 min at 37 C, followed by centrifugation at 100,000 g for 60 min at 25 C. This treatment resulted in solubilization of 94% of the alkaline phosphohydrolase, 91% of the phosphodiesterase and ribonuclease, and 88% of the 5'-nucleotidase activities. The pH optima for enzymes solubilized in nonionic and ionic detergents (Triton and sodium dodecyl sulfate, respectively) did not differ. Isoelectric focusing of the Triton-solubilized material demonstrated the presence of at least 14 polypeptides, a majority of which had isoelectric points below pH 7.
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PMID:Solubilization of the membrane-bound enzymes of the brush-border plasma membrane of Hymenolepis diminuta (Cestoda) using nonionic detergents. 628 6

The phosphomannosyl recognition marker of acid hydrolases, which mediates their translocation to lysosomes, has been shown to be synthesized in two steps. First, N-acetylglucosamine 1-phosphate is transferred to an acceptor mannose by UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, resulting in a phosphate group in diester linkage between the outer N-acetylglucosamine and the inner mannose. Next, an a-N-acetylglucosaminyl phosphodiesterase removes the N-acetylglucosamine, leaving the phosphate in monoester linkage with the underlying mannose residue. This exposed phosphomannosyl residue serves as the essential component of a recognition marker which leads to binding to high-affinity receptors and subsequent translocation to lysosomes. We propose that the first enzyme in this scheme, N-acetylglucosaminylphosphotransferase, catalyses the initial, determining step by which newly synthesized acid hydrolases are distinguished from other newly synthesized glycoproteins and thus are eventually targeted to lysosomes. The absence of this enzyme activity, as in inclusion-cell (I-cell) disease and pseudo-Hurler polydystrophy, precludes the receptor-mediated targeting of newly synthesized acid hydrolases to lysosomes. As a consequence, the enzymes are secreted into the extracellular milieu.
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PMID:Steps in the phosphorylation of the high mannose oligosaccharides of lysosomal enzymes. 629 19

The properties of a teichoic acid degrading enzyme (teichoicase) isolated from Bacillus subtilis Marburg are described. The purified enzyme showed phosphodiesterase activity but not phosphomonoesterase activity, and it had an absolute substrate specificity for alpha-glucosylated glycerol teichoic acid, the endogenous cell wall teichoic acid of the enzyme-producing cell. The substrate was degraded by an exo-mechanism yielding the monomer alpha-D-glucose 1 leads to 2 (sn)glycero-3-phosphate. When B. subtilis Marburg was grown in a rich medium, enzyme activity was detected in extracts from sporulating cells. Teichoicase activity was present in a mutant blocked in stage II of the sporulation process but was absent in a mutant blocked in stage O. It was concluded that teichoicase is active on enzyme-producing cells since the reaction product could be detected in their culture supernatant. Attempts to demonstrate analogous enzyme activity in other Bacillus strains failed. The enzyme could be used for the rapid detection of alpha-glucosylated glycerol teichoic acid and for the controlled alteration of native bacterial cell surfaces exhibiting the appropriate structure.
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PMID:Teichoicase from Bacillus subtilis Marburg. 630 14

Macrophages have been obtained from the peritoneal cavities of C57BL/6 mice following treatment with C. parvum, MVE-2, mineral oil, or thioglycollate. Cell populations were primarily composed of mononuclear phagocytes as determined by a latex bead uptake assay. Macrophages obtained from C. parvum or MVE-2 were activated as judged by enhanced cytostatic activity against two tumor cell target lines. Thioglycollate-elicited macrophages demonstrated much lower cytostatic ability. Rats were immunized with activated MVE-2 macrophages. Hybridomas were prepared by fusion with a non-secreting myeloma cell line followed by cloning. Cell supernates were selected on the basis of binding to activated but not elicited macrophages. The monoclonal antibody produced has been characterized by flow cytometry. The antibody does not react with syngeneic erythrocytes, thymocytes, or spleen cells. Reaction with thioglycollate macrophages is very low. Alternatively, intense binding is found on activated macrophages. This antigen which accompanies macrophage activation for tumor cell cytostasis is designated as macrophage activation antigen-1 (MAA-1). Several important physiological changes accompany the process of macrophage activation. For example, activated macrophages demonstrate enhanced microbicidal, phagocytic, secretory, and tumoricidal activity (for reviews see refs. 1,2). Concommitant alterations in cell surface properties have been observed. These include: (a) changes in surface morphology and spreading (3-5), (b) altered lipid and protein content (6,7), (c) decreases in 5'-nucleotidase activity and alkaline phosphodiesterase (8), increases in leucine aminopeptidase (8), decreases in mannose receptors (11,12), and antigen F4/80 (11), (d) increases in Ia antigens (11,12), and (e) increased tumor cell binding (13). These structural and functional modifications indicate that activated macrophages represent a unique class of functionally differentiated cells (9). Antigenic modifications accompanying macrophage differentiation are of special interest. Markers for specific macrophage classes might be useful in defining differentiation pathways, dissecting type-specific functional activities such as tumor cytotoxicity, and providing a means to identify macrophage subsets in heterogeneous cell populations. In the present work we have taken the first step in this direction by defining a cell surface macrophage activation antigen.
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PMID:Characterization of a monoclonal antibody defining a macrophage activation-specific cell surface antigen. 674 39

Human monocytes cultured on surface-bound immune complexes exhibited a loss of ability to form rosettes with IgG-sensitized sheep erythrocytes (EA). This loss was not a result of inhibition of Fc receptors by solubilized complexes nor of release of soluble factors by the cells. Loss of EA rosetting was not prevented by culture of monocytes at 4 degrees C, or by treatment with colchicine, cytochalasin B, or local anethetic agents. These results suggested that the loss was not secondary to capping or interiorization of Fc receptors. The results of other studies indicated that the Fc receptors were not damaged by lysosomal enzymes or oxygen radicals. Maintenance of EA rosetting ability of monocytes cultured on surface-bound immune complexes was seen after a 3-h preincubation of the cells in 100 mM 2-deoxy-D-glucose (2dG). A similar preincubation in ATP or in 8-bromoadenosine 3':5'-cyclic monophosphoric acid plus the phosphodiesterase inhibitor methyl isobutyl xanthine led to a partial loss of EA rosetting of cells on plain fibrin and to a partial reversal of the effects of 2dG seen with cells on complexes. We conclude that EA rosetting of monocytes cultured on surface-bound immune complexes is reduced by cyclic nucleotide-mediated effects on Fc receptor number or function.
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PMID:Loss of Fc receptor activity after culture of human monocytes on surface-bound immune complexes. Mediation by cyclic nucleotides. 735 Feb 48

Leptospiral lipopolysaccharides (LPS) are the main antigens responsible for immunity in leptospirosis. In this investigation we studied the nature of the antigenic determinants of LPS extracted from Leptospira interrogans serovar hardjo (reference strain Hardjoprajitno). The reactions of anti-LPS monoclonal antibodies (mAbs) MUM/F1-4/hardjo (IgM) and MUM/F1-6/hardjo (IgG) with whole cell lysates in Western immunoblotting analysis were unaffected by proteinase K treatment. Periodate treatment of the LPS destroyed the binding of MUM/F1-6/hardjo but preserved that of MUM/F1-4/hardjo. Alkaline phosphatase decreased significantly the binding of MUM/F1-4/hardjo to the LPS but only slightly that of MUM/F1-6/hardjo. On the other hand, phosphodiesterase totally destroyed the binding capacity of both monoclonal antibodies in enzyme immunoassays (EIA). A number of mono- and oligosaccharides was used in EIA inhibition studies. Mannose-6-phosphate and galactose-6-phosphate inhibited the binding of MUM/F1-4/hardjo (50% inhibition at a concentration of 5 mM) to the antigen, but glucose-6-phosphate did not. Galactosamine and mannosamine inhibited the binding of MUM/F1-6/hardjo (50% inhibition at a concentration of 3-4 mM), whereas only a weak inhibition was observed with glucosamine. In contrast, N-acetylated amino sugars did not show any inhibition. An O-acetyl group also appears to be involved in the antigen-antibody binding process.
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PMID:Immunochemical studies of opsonic epitopes of the lipopolysaccharide of Leptospira interrogans serovar hardjo. 751 91

The influence of the main flavonoids from Crataegus species (hawthorn, Rosaceae) on coronary flow, heart rate and left ventricular pressure as well as on the velocity of contraction and relaxation was investigated in Langendorff perfused isolated guinea pig hearts at a constant pressure of 70 cmH2O. Drug action was evaluated in a concentration range of 10(-7) to 5 x 10(-4) mol/l. An increase of coronary flow caused by the O-glycosides luteolin-7-glucoside (186%), hyperoside (66%) and rutin (66%) as well as an increase of the relaxation velocity (positive lusitropism) by luteolin-7-glucoside (104%), hyperoside (62%) and rutin (73%) were the major effects observed at a maximum concentration of 0.5 mmol/l. Furthermore, slight positive inotropic effects and a rise in heart rate were seen. Similar but less intensive actions were found with the C-glycosides vitexin, vitexin-rhamnoside and monoacetyl-vitexin-rhamnoside. Possible beta-adrenergic activities of the flavonoids could be excluded by the addition of propranolol in fixed concentrations of 10(-8) to 10(-5) mol/l. Moreover, pretreatment of the animals with reserpine (7 mg/kg) did not influence myocardial activity of hyperoside (10(-4) mol/l). As previous experiments showed an inhibition of the 3',5'-cyclic adenosine monophosphate phosphodiesterase, the results suggest an inhibition of this enzyme as the possible underlying mechanism of cardiac action of flavonoids from Crataegus species.
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PMID:Myocardial effects of flavonoids from Crataegus species. 757 43

Metabolic labelling experiments performed with cultured pituitary lactotrophes revealed the presence of a glycosyl-phosphatidylinositol (GPtdIns) structurally related to GPtdIns lipids isolated from other cell types as demonstrated by: (i) metabolic incorporation of [3H]galactose, [3H]glucosamine and [3H]inositol into the polar inositolphosphoglycan moiety (InsPG) and [3H]myristate and [3H]palmitate into the diacylglycerol (DAG) backbone of GPtdIns; (ii) sensitivity of the [3H]labelled GPtdIns to nitrous acid deamination and; (iii) sensitivity of GPtdIns to phosphatidylinositol (PtdIns)-specific phospholipase C (PLC) hydrolysis. In cultured pituitary cells labelled to isotopic steady state with 10 microCi/ml of [3H]glucosamine, treatment with hypothalamic TRH (10(-6) M) induced a rapid and transient hydrolysis (ca. 50%) of the labelled GPtdIns. Moreover, as demonstrated in [3H]inositol labelled cells, treatment with thyrotropin releasing hormone (TRH) elicited the cleavage of [3H]GPtdIns in a similar manner, and this effect was followed by the phosphoinositide (PtdIns, PtdInsP and PtdInsP2) hydrolysis 30 s later. These results suggest that the phosphodiesterase cleavage of GPtdIns could be an early event implicated in TRH action in pituitary lactotrophes.
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PMID:Partial characterization of a thyrotropin releasing hormone-sensitive glycosyl-phosphatidylinositol in pituitary lactotrophes. 761 97


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