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)

Fetal lung cyclic AMP phosphodiesterase, cyclic AMP, phosphatidyl choline, and incorporation of precursors into phosphatidyl choline were measured in rabbits after maternal administration of hydrocortisone phosphate and aminophylline. Both agents inhibited lung phosphodiesterase activity and augmented cyclic AMP concentrations (Table 1). Aminophylline administration was associated with a significant increase in lung saturated phosphatidyl choline (Table 2). Incorporation of [14C] choline and [3H] methionine was increased by both aminophylline and hydrocortisone (Table 3).
 ...
PMID:Role of adenosine 3', 5'-monophosphate in maturation of fetal lungs. 17 50

The bacteriostatic effect of methioninyl adenylate(MAMP)--a specific inhibitor of the enzyme methionyl-tRNA synthetase--was investigated on Salmonella typhimurium and Pseudomonas aeruginosa. 0.1 mM of this molecule added to the culture, inhibits the growth of S. typhimurium. The inhibition is specifically reversible by 0.1 mM L-methionine. In the same conditions even 1-2 mM MAMP has a very slight effect on the growth rate of P. aeruginosa and only during the first two generations. The same observation was made with the two other members of the fluorescens group P.fluorescens and P.putida. The growth rate of P. testosteroni with 1 mM MAMP in the medium is similar to the growth rate of P. aeruginosa but the other member of the acidovorans group P. acidovorans is much more affected by the smae concentration of the inhibitor. --P. multivorans is inhibited by MAMP like P. acidovorans but with a somewhat higher yield at the end of the culture. --MAMP has no effect on P. alcaligenes. The possible reasons for the weak bacteriostatic effect of MAMP on P. aeruginosa were investigated. It was established that the inhibitor enters the cells and is not used as a carbon and energy source. The intracellular methionine concentration in S. typhimurium and in P. aeruginosa is about the same and does not increase when bacteria are cultivated with MAMP. The MTS of the two microorganisms is inhibited by MAMP in vitro to about the same extent. Furthermore the tRNAmet from P. aeruginosa are fully acylated after 3 to 4 generations with this compound. Nevertheless MAMP elicits higher MTS activity in P. aeruginosa and in P. acidovorans after 1 h of incubation. The most striking difference between S. typhimurium and P. aeruginosa is that the intra and extracellular level of 5'phosphodiesterase which degrades MAMP is 10-20 fold higher in the second than in the first species.
 ...
PMID:Comparative effect of methioninyl adenylate on the growth of Salmonella typhimurium and Pseudomonas aeruginosa. 18 17

Methionyl adenylate (Met-AMP) inhibits protein synthesis by interacting with methionyl-tRNA synthetase. Addition of 1--3 mM inhibitor to chick embryo fibroblasts rapidly stops protein synthesis and DNA synthesis but not RNA synthesis. These effects can be reversed by renewal of the medium. The extent and reversibility of protein and DNA syntheses depend on the concentration of MetAMP in the cultures, the length of exposure and the cellular density. MetAMP is recognised by several enzymes as substrate and/or as inhibitor. MetAmp is degraded to methionol plus 5'-adenylic acid by 5'-phosphodiesterase. Adenosine deaminase, adenylic acid deaminase and 3':5'-phosphodiesterase cannot use MetAMP as substrate but the last enzyme is inhibited. The presence of MetAMP in cultures provokes a small but reproducible increase in the level of methionyl-tRNA synthetase and 5'-phosphodiesterase.
 ...
PMID:Further studies of the action of methionyl adenylate on chick embryo fibroblasts. 19 96

The mechanism of action of lutropin on the stimulation of the synthesis of a specific lutropin-induced protein in rat testis Leydig cells was investigated. Lutropin-induced protein has a mol.wt. of approx. 21000 and is detected by labelling the Leydig-cell proteins with [(35)S]methionine, followed by separation by polyacrylamide-gel electrophoresis and radioautography of the dried gel. The incorporation of (35)S into lutropin-induced protein was used as an estimate for the synthesis of the protein. Incubation of Leydig cells with dibutyryl cyclic AMP or cholera toxin also resulted in the stimulation of synthesis of the protein. Synthesis of lutropin-induced protein, when maximally stimulated with 100ng of lutropin/ml, could not be stimulated further by addition of dibutyryl cyclic AMP. Addition of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, further increased synthesis of the protein in the presence of a submaximal dose of lutropin (10ng/ml) but not in the absence of lutropin or with maximal amounts of lutropin (100 and 1000ng/ml). Actinomycin D prevented the effect of lutropin on the stimulation of lutropin-induced protein synthesis when added immediately or 1h after the start of the incubation, but not when added after 5-6h. This is interpreted as reflecting that, after induction of mRNA coding for lutropin-induced protein, lutropin had no influence on the synthesis of the protein in the presence of actinomycin D. Synthesis of the protein was also stimulated in vivo by injection of choriogonadotropin into rats 1 day after hypophysectomy, and the time course of this stimulation of lutropin-induced protein synthesis in vivo was similar to that obtained by incubating Leydig cells in vitro with lutropin. From these results it is concluded that stimulation of lutropin-induced protein synthesis by lutropin is most probably mediated by cyclic AMP and involves synthesis of mRNA.
 ...
PMID:Regulation of the synthesis of lutropin-induced protein in rat testis Leydig cells. 20 2

Methionine residues have been implicated in the activation of cyclic nucleotide phosphodiesterase by the Ca2+-dependent protein modulator [Walsh, M., & Stevens, F.C. (1977) Biochemistry 16,2742-2749]. Treatment of the modulator with N-chlorosuccinimide in the presence of Ca2+ resulted in selective oxidation of methionine residues at positions 71,72, 76, and, possibly, 109 in the modulator sequence. These residues lie on the surface of the molecule exposed to solvent. This modification has several effects on the modulator protein: (1) the Ca2+-binding properties of the oxidized modulator are changed with apparent loss of high-affinity binding sites, (2) the oxidized protein no longer interacts with phosphodiesterase, and (3) troponin C like activities, viz., Ca2+-dependent change in mobility on urea-polyacrylamide gel electrophoresis and formation of a urea-stable complex with troponin I, are lost upon oxidation of the modulator. The phosphodiesterase binding domain of the modulator protein appears to be located between the second and third Ca2+-binding loops, a region of the molecule known from previous partial proteolysis studies [Walsh, M., Stevens, F.C., Kuznicki, J., & Drabikowski, W.(1977), J. Biol. Chem. 252, 7440-7443] to be exposed in the presence of Ca2+.
 ...
PMID:Chemical modification studies on the Ca2+-dependent protein modulator: the role of methionine residues in the activation of cyclic nucleotide phosphodiesterase. 21 97

The methylation of cytoplasmic ribosomal RNA of cultured sycamore cells (Acer pseudoplatanus L.) was investigated. Labelled 17-S and 26-S rRNA were prepared from cells that had been incubated with either [32P]phosphate, [Me-3H]methionine or [Me-14C]methionine. Ion-exchange resin chromatography of 0.3 M KOH or 1 M HCl hydrolysates and two-dimensional chromatographic analyses of phosphodiesterase plus phosphatase digests of 17-S and 26-S rRNA were performed. 17-S and 26-S rRNA contain 49 and 91 methyl groups per molecule, respectively. These values were verified in sevemral ways. The high degree of methylation of sycamore rRNA, particularly for the 26-S rRNA, contrasts with the situation in all other investigated organisms. Several methylated bases were identified. 7-Methylguanine and 5-methylcytosine both occur in 17-S and 26-S rRNA. N6-Methyladenine and N6,N6-dimethyladenine are restricted to the 17-S rRNA while 3-methyluracil and 1-methyladenine occur in the 26-S rRNA. One hypermodified uridine was also tentatively identified in the small rRNA. In 17-S rRNA, there is one copy of 7-methylguanine, N6-methyladenine and hypermodified uridine and two copies of N6,N6-dimethyladenine. 3-Methyluracil, 1-methyladenine and 5-methylcytosine occur twice, twice and three times, respectively, in 26-S rRNA. 7-Methylguanine and 5-methylcytosine are only in submolar amounts in the 26-S and 17-S rRNA, respectively. There are 40 +/- 2 and 83 +/- 3 2'-O-methylriboses per 17-S and 26-S rRNA molecule, respectively. In addition to the four 2'-O-methylnucleosides, one 2'-O-methylpseudouridine is present in the 17-S rRNA. Several lines of evidence argues for a non-random distribution of the methylriboses. In particular, one and seven Nm-Nm-Np structures occur in the 17-S and 26-S rRNA, respectively. The data are discussed comparatively with the methylation pattern of Escherichia coli, yeast and HeLa cell rRNA.
 ...
PMID:Studies on the methylation of cytoplasmic ribosomal RNA from cultured higher plant cells. 22 45

The effect of adenylate cyclase activators on C5a- and f-Met-Leu-Phe-induced human neutrophil aggregation, enzyme release and superoxide production was investigated. C5a-stimulated superoxide production was markedly inhibited by adenylate cyclase activators, and the order of potency was PGE1 greater than isoproterenol greater than epinephrine greater than PGF2 alpha, which correlated with intracellular cAMP levels. However, neutrophil aggregation was inhibited by PGE1, PGE2, isoproterenol and epinephrine only at concentrations greater than 10(-6) M. Lysozyme release was inhibited only via PGEs in the presence of the phosphodiesterase inhibitor, methylisobutylxanthine. These results suggest that in the human neutrophil: (1) C5a-induced superoxide production is more sensitive to regulation by cAMP than neutrophil aggregation or enzyme release, and (2) the type of receptor occupied as well as the threshold level of cAMP are important in the regulation of neutrophil aggregation and enzyme release stimulated by C5a.
 ...
PMID:Effect of adenylate cyclase activators on C5a-induced human neutrophil aggregation, enzyme release and superoxide production. 137 1

The purpose of this study was to determine whether the selective type IV cAMP-phosphodiesterase inhibitor rolipram could reduce the reperfusion injury that occurs during myocardial infarction in the anesthetized dog. This question was tested in pentobarbital-anesthetized dogs subject to 90 min of regional myocardial ischemia and 5 h of reperfusion. Dogs were treated with 1 mg/kg of rolipram (i.v., 15 min before reperfusion) followed by a 1 mg/kg/h infusion over the duration of the 5 h of reperfusion. Rolipram was tested in vitro for efficacy in inhibition of isolated human neutrophil superoxide generation. Rolipram produced significant inhibition of superoxide production over the concentration range of 0.1-100 microM rolipram when neutrophils were stimulated with a 10(-7) M concentration of the chemotactic peptide f-Met-Leu-Phe. Rolipram significantly inhibited superoxide generation from human and canine granulocytes in whole blood stimulated by zymosan. Therapeutic concentrations of rolipram in the blood of dogs were achieved during the course of the experiments with a plasma concentration of 0.761 +/- 0.095 micrograms/ml (2.76 +/- 0.34 microM) at the time of reperfusion, and 0.574 +/- 0.098 micrograms/ml (2.08 +/- 0.36 microM) at the end of the reperfusion period. The relative severity of myocardial ischemia between the two treatment groups was similar as assessed with radiolabeled microsphere measurement of myocardial blood flow. Transmural myocardial blood flows were not significantly different between the two groups after coronary occlusion (control, 0.05 +/- 0.01 ml/min/g, n = 6, vs. rolipram, 0.18 +/- 0.07 ml/min/g, n = 6; p = 0.48).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inhibition of granulocyte cAMP-phosphodiesterase by rolipram in vivo is not sufficient to protect the canine myocardium from reperfusion injury. 137 23

Epidermal cells from psoriatic lesions demonstrate a very low cAMP response to beta-adrenergic stimuli. We have shown that a similar abnormality occurs in dermal fibroblasts from affected areas of skin. The cells, after 5-12 passages in tissue culture, had a much reduced response to 10(-8) M and 10(-6) M isoproterenol when compared with fibroblasts from control subjects. The abnormality was not abolished by the addition of the phosphodiesterase inhibitor, 3-isobutyl-I-methylxanthine. Other putative agonists tested were vasoactive intestinal peptide and peptide histidine methionine. Neither of these had an effect on dermal fibroblasts from either normal controls or from lesions of psoriasis.
 ...
PMID:Beta-adrenergic stimulation of cyclic AMP is defective in cultured dermal fibroblasts of psoriatic subjects. 169 75

Several species-specific monoclonal antibodies (T11, T13-T15) which only react with Leishmania tropica, recognize phosphorlated carbohydrate epitopes on lipophosphoglycan and the structurally related molecule, phosphoglycan, which is shed by promastigotes into spent culture medium. During immunoaffinity isolation of [32P]orthophosphate-labeled phosphoglycan on monoclonal antibody T15 conjugated to Sepharose 4B, a high-Mr component (approx. 200,000) was co-purified. The latter material is metabolically labeled with [35S]methionine and [3H]glucosamine. This glycoprotein was separated from phosphoglycan by chromatography on lentil lectin resin. The glycoprotein exhibited a L-tatrate-sensitive acid phosphatase activity, typical of secreted acid phosphatase (EC 3.1.3.2) from Leishmania. Monospecific antibodies to Leishmania donovani-secreted acid phosphatase selectively precipitated the L. tropica enzyme from immunoaffinity purified mixtures of the two antigens, and monoclonal antibodies to lipophosphoglycan precipitate the pure enzyme. Species-specific monoclonal antibodies to L. major lipophosphoglycan also recognized both L. tropica antigens. Treatment of the acid phosphatase with periodate or phosphodiesterase I abolished binding by the monoclonal antibodies to the pure enzyme. These results demonstrate that the two major secreted glycoconjugates of Leishmania tropica, the lipophosphoglycan and the acid phosphatase, share species-specific phosphorylated carbohydrate epitope(s).
 ...
PMID:Lipophosphoglycan and secreted acid phosphatase of Leishmania tropica share species-specific epitopes. 169 35


1 2 3 4 5 6 7 8 9 Next >>