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:3.1.3.5 (5'-nucleotidase)
3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane function was examined in cultured cells from cystic fibrosis patients by assaying several enzymes on intact skin fibroblasts attached to culture dishes. This technique required few cells and minimized disruption of cellular organization. Comparison of enzyme activities of intact and broken cells showed that 12% of total glucose-6-phosphate dehydrogenase, a cytoplasmic enzyme, was measurable using intact cells, while all adenosine monophosphatase was measurable using intact cells. Alkaline paranitrophenylphosphatase activity was divided between the cell surface and interior. Substrate competition experiments indicated that substrate specificities for adenosine monophosphatase and paranitrophenylphosphatase activities were different. Adenosine monophosphatase activities of 2 control and 2 cystic fibrosis strains fluctuated similarly during the cell culture cycle. The apparent Km values relative to adenosine monophosphate were similar in all strains. A chromatographic fraction of serum from a cystic fibrosis patient that was inhibitory to oyster ciliary activity had no effect on adenosine monophosphatase activity of normal fibroblasts. Furthermore, fractions of media from cystic fibrosis homozygote and heterozygote fibroblast cultures were not inhibitory to adenosine monophosphatase activities of intact normal fibroblasts or of part iculate fractions prepared from them. In light of previous studies that showed that factors from cystic fibrosis serum of culture medium disrupted specific membrane activities, it is proposed that the cystic fibrosis factor interacts with the plasma membrane, interfering most conspicuously with the protein functions that are sensitive to changes in their membrane environment.
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PMID:Surface enzymes in cultured fibroblasts from cystic fibrosis patients. 18 10

Submaxillary glands of rats, chronically treated with isoproterenol or reserpine undergo morphological and functional alterations. These changes have been described to resemble those seen in human cystic fibrosis. Since it has been proposed that the beta adrenergic-mediated response is altered in exocrine glands of cystic fibrosis patients, we have examined whether the drug-induced alterations in rat salivary glands were accompanied by changes in the numbers and affinities of beta adrenergic receptor sites. Beta receptor characteristics were determined by means of direct binding studies with the beta adrenergic antagonist [3H]dihydroalprenolol. Compared to controls, specific binding capacities of [3H]dihydroalprenolol per unit of protein increased by 110 +/- 14% after reserpine treatment and decreased by 34 +/- 11% after isoproterenol administration (P less than .001). The difference in the number of receptor sites remained statistically significant whether expressed per gram of fresh weight or per unit of the membrane marker 5'-nucleotidase activity. Dissociation constants of the binding were not significantly different between the treatment groups. The observed changes in the number of beta receptors showed an inverse relationship to the drug-induced presumed changes of catecholamine concentrations at the receptor sites. This suggests the existence of a feedback system which maintains the balance within the autonomous nervous system. We speculate that in cystic fibrosis this adaptive system is genetically abnormal.
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PMID:Changes in beta adrenergic receptors in submaxillary glands of chronically reserpine- or isoproterenol-treated rats. 625 91

Luminal extracellular ATP evoked a bumetanide-sensitive short-circuit current in cultured T84 cell epithelia (90.2 +/- 18.2 microA/cm2 at 100 microM ATP, apparent 50% effective concentration, 11.5 microM). ATP appeared to increase the Cl- conductance of the apical membrane but not the driving force for Cl- secretion determined by basolateral membrane K+ conductance. Specifically, the magnitude of Cl- secretion stimulated by ATP was independent of basal current, and forskolin pretreatment abolished subsequent stimulation of Cl- secretion by ATP. Whereas ATP stimulated modest production of adenosine 3',5'-cyclic monophosphate (cAMP) by T84 cells, ATP caused smaller increases in intracellular Ca2+ and inositol phosphate activities than the Ca(2+)-signaling Cl- secretagogue carbachol. An inhibitor of 5'-nucleotidase, alpha,beta-methyleneadenosine 5'-diphosphate, blocked most of the response to luminal ATP. The adenosine receptor antagonist 8-(p-sulfophenyl)theophylline blocked both the luminal ATP-dependent generation of cAMP and Cl- secretion when administered to the luminal but not submucosal bath. These results demonstrate that the Cl- secretion stimulated by luminal ATP is mediated by a A2-adenosine receptor located on the apical cell membrane. Thus metabolism of extracellular ATP to adenosine regulates the activity of cystic fibrosis transmembrane conductor regulator (CFTR) in the apical membrane of polarized T84 cells.
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PMID:Activation of CFTR Cl- conductance in polarized T84 cells by luminal extracellular ATP. 753 59

Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis (CF). Preliminary data suggest that ursodeoxycholic acid (UDCA) may be beneficial for treatment of this manifestation. We performed a double-blind, multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides standard liver function tests. We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA. From June to December 1990, we enrolled in 12 centers 55 CF patients with liver disease (39 male subjects; median age, 13.8 years). They were randomly assigned to receive for 1 year one of the following treatments: UDCA (15 mg/kg body weight daily) plus taurine (30 mg/kg body weight daily), UDCA plus placebo, placebo plus taurine, or double placebo. Clinical and laboratory evaluations were performed every 3 months. After 1 year, deterioration of overall clinical conditions, as indicated by the Shwachman-Kulczycki score (SKS), occurred in patients who received placebo but not in those who received UDCA (P = .025). Patients treated with UDCA also showed an improvement in gamma-glutamyl transpeptidase (GGT) (P = .004) and 5'-nucleotidase (P = .006) levels. Treatment with taurine was followed by a significant increase in serum prealbumin levels (P = .053), a trend toward a reduction in fat malabsorption, and no effect on the biochemical profile. No severe side effects occurred with any treatment. Thus, we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease. Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status.
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PMID:Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis. 867 68

We demonstrate that a mucoid, alginate-producing strain of Pseudomonas aeruginosa isolated from the lungs of a cystic fibrosis (CF) patient secretes multiple enzymes with nucleoside diphosphate kinase (Ndk), ATPase, adenylate kinase, 5'-nucleotidase, and ATP-modifying enzymatic activities. The secretion is triggered at high cell density and in complex media but is greatly reduced when the mucoid cells are grown in mineral salts media or in presence of 5.0 mM Ca2+ or Mg2+. Interestingly, the secretion is triggered primarily in the mucoid CF isolate of strain 8821M (or in strain FRD1) but not in a nonmucoid laboratory strain, PAO1. The purified secreted Ndk shows 100% match in its N-terminal amino acid sequence with that of purified intracellular Ndk and demonstrates similar enzymatic properties. The N-terminal sequence of the purified ATPase isolated from an ndk knockout mutant shows its identity with that of the heat shock chaperonin Hsp60. During fractionation, the flowthrough fraction from a Mono Q column demonstrates the presence of 5'-nucleotidase, adenylate kinase, and a putative ATP reductase activity. These fractions demonstrate high cytotoxic activities for murine peritoneal primary macrophages which can be further stimulated in the presence of ATP or inhibited by pretreatment of macrophages with oxidized ATP (oATP). The cytotoxicity associated with ATP-induced stimulation is believed to be due to activation of macrophage surface-associated P2Z (P2X7) receptors, which are one of the purinergic receptors responsible for pore formation on macrophage membrane. Blocking of these receptors by pretreatment with oATP blocks ATP-induced macrophage cell death. Thus mucoid P. aeruginosa cells elaborate enzymes that modulate the external ATP levels of macrophages, thereby modulating macrophage cell death through P2Z receptor activation. Evidence for the presence of secreted cytotoxic agents that act independently of P2Z receptor activation is also presented.
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PMID:P2Z-Independent and P2Z receptor-mediated macrophage killing by Pseudomonas aeruginosa isolated from cystic fibrosis patients. 1049

Burkholderia cepacia is an emerging opportunistic pathogen that causes fatal infections in patients suffering from cystic fibrosis (CF) and chronic granulomatous disease. Various environmental isolates of B. cepacia are, however, capable of degrading environmental pollutants, such as trichloroethylene, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), etc., and are also highly effective in controlling plant diseases caused by nematodes and fungi. Such strains have therefore been proposed for environmental release to clean up toxic dump sites or as biopesticides. Various efforts to distinguish between clinical and environmental isolates of B. cepacia with regard to their virulence characteristics have produced ambiguous results, suggesting that newer methods are needed to test for the presence or absence of pathogenic potential in B. cepacia strains proposed for environmental release. We now report that several clinical strains of B. cepacia secrete cytotoxic factors that allow macrophage and mast cell death in the presence of external ATP. Several environmental strains had reduced activity in this regard. We also demonstrate that, while all the strains secrete enzymes that have nucleoside diphosphate kinase (Ndk), adenylate kinase (Ak) and 5'-nucleotidase activity, the level of secretion of the 5'-nucleotidase (and/or ATPase/phosphatase) appears to be lower in the environmental strains than in the clinical strains. The secretion of these enzymes is specifically activated in the presence of eukaryotic proteins such as alpha2-macroglobulin. As macrophage-or mast cell surface-associated P2Z receptors promote their cell death in the presence of mM concentrations of ATP, and as the secreted ATP-using enzymes generate various phosphorylated or non-phosphorylated adenine nucleotides that may even be better agonists than ATP in activating the P2Z receptors or may act through the activation of additional purinergic receptors, such enzymes may play an important role in allowing B. cepacia to evade host defence.
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PMID:Clinical and environmental isolates of Burkholderia cepacia exhibit differential cytotoxicity towards macrophages and mast cells. 1093 Dec 97

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