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)

Several studies have found high cAMP content in hepatomas in vivo, while hepatoma cells in vitro have very low levels. To explore this discrepancy and the regulation of cAMP in hepatomas, we have examined the cell line MH1C1 from Morris hepatoma 7795. These cells in culture contained low intracellular cAMP concentrations (approximately 0.5 pmol/mg protein at confluency), and were unresponsive to glucagon and prostaglandins (PG) E1 and E2. In contrast, solid hepatomas in rats developed from inoculates of MH1C1 had a 40-fold higher basal cAMP concentration and were stimulated by PGE1 and PGE2. Fibroblasts cultured from these tumours also contained high cAMP levels and responded strongly to PGE1. This may suggest that the difference in cAMP regulation between hepatomas in vivo and hepatoma cells in vitro results from the presence of other cells in the solid tumour rather than from selection of low-cAMP cells during the cloning procedure. Low-Km and intermediate-Km cAMP phosphodiesterase activity was high in MH1C1, compared to normal hepatocytes. This might contribute to the low cAMP level. The ability of MH1C1 to form cAMP was not defective, as the level could be increased more than 200-fold by beta-adrenergic activation in the presence of the phosphodiesterase inhibitor methylisobutylxanthine.
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PMID:The regulation of cyclic AMP levels in cultured MH1C1 rat hepatoma cells and in solid tumours derived from MH1C1 cell inoculates. 303 96

The effect of dexamethasone on adenosine 3',5'-monophosphate (cAMP) phosphodiesterase activity in cultured HTC hepatoma cells was investigated. Homogenates of these cells contain phosphodiesterase activity with two apparent Michaelis constants for cAMP (2-5 mum and 50 mum). At all substrate concentrations tested, phosphodiesterase activity was decreased 25-40% in cells incubated for 36 hr or more with 1 mum dexamethasone. Acid phosphatase activity in the same cells was not decreased. alpha-Methyl testosterone, 1 mum, was without effect on phosphodiesterase activity. Incubation for 10 min with epinephrine plus theophylline increased the cAMP content of the HTC cells 3- to 6-fold. In cells incubated for 72 hr with dexamethasone, the basal concentration of cAMP was slightly increased and the increment produced by epinephrine plus theophylline was markedly increased. We believe that in many cells the so-called permissive effects of steroid hormones on cAMP mediated processes may be due to an effect of these hormones on cAMP phosphodiesterase activity similar to that observed in HTC cells incubated with dexamethasone.
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PMID:An effect of dexamethasone on adenosine 3',5'-monophosphate content and adenosine 3',5'-monophosphate phosphodiesterase activity of cultured hepatoma cells. 434 39

The cAMP phosphodiesterase activity in mouse hepatomas 46, 61 and 22A is established to be lower than in the normal liver. Sensitivity of enzymes to inhibitors in tumours is also lower. Dibutyryl-cAMP inhibits the growth of hepatoma 46 and leads to an increase in the functional activity of tumour cells.
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PMID:[Adenosine cyclic-3',5'-monophosphate phosphodiesterase in hepatomas with different growth rates]. 609 46

In rat hepatoma cells the synthetic glucocorticoid dexamethasone causes a 3-fold increase in the activity of the plasma membrane enzyme alkaline phosphodiesterase I (oligonucleat 5'-nucleotidohydrolase, EC 3.1.4.1). The data are consistent with an induction phenomenon mediated by the glucocorticoid receptor involved in tyrosine aminotransferase induction. The effect on alkaline phosphodiesterase I is not a reflection of a general membrane effect of dexamethasone, because the activity of three other enzymes of the plasma membrane is unaffected. On the other hand, nucleoside diphosphatase (nucleoside diphosphate phosphohydrolase acting on ADP) activity is inhibited. Thus, two more enzymes sensitive to glucocorticoids have been identified in a cell line in which these hormones influence only very few gene products. This paper describes enzymatic changes in the plasma membrane of rat hepatoma cells in which glucocorticoids normalize a number of membrane-associated processes that are considered to be characteristic of transformed cells.
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PMID:Glucocorticoid hormones increase the activity of plasma membrane alkaline phosphodiesterase I in rat hepatoma cells. 610 83

The following evidence suggests that inhibition of hepatoma cell (HTC) growth by cyclic nucleotides is an adenosine-like effect that is greatly modified by the type and treatment of serum used in the culture medium and is probably not mediated by cyclic AMP-dependent protein kinase: 1) Heating serum reduces its phosphodiesterase content, thereby slowing metabolism of cyclic AMP and reducing the inhibition of HTC cell growth by cyclic AMP; 2) Using medium that contains phosphodiesterase but lacks adenosine deaminase causes adenosine to accumulate from cyclic AMP and increases the toxicity of cyclic AMP; 3) Uridine or cytidine reverses the growth inhibition caused by adenosine, 5'-AMP or cyclic AMP; 4) adenosine, 5'-AMP and N6-(delta 2-isopentenyl) adenosine are more toxic for HTC cells than is cyclic AMP, and N6,O2-dibutyryl cyclic AMP is not toxic; and 5) N6,O2'-dibutyryl cyclic AMP inhibits growth of Reuber H35 cells, but uridine prevents this inhibition of growth. We conclude that most, if not all, of the inhibitory effects of cyclic AMP and N6,O2'-dibutyryl cyclic AMP on HTc and Reuber H35 hepatoma cell growth are due to the generation of toxic metabolites.
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PMID:Inhibition of hepatoma cell growth by analogs of adenosine and cyclic AMP and the influence of enzymes in mammalian sera. 612 49

2,131 coded sera were obtained and tested according to the new 5'-NPDase-V isozyme test. On decoding, 99/126 (79%) samples of primary hepatoma, from the United States and other countries, were positive. In the U. S. group, 51/58 (88%) were positive, 23/58 (40%) had AFP higher than 20 ng/ml. In the non-U. S. group, 48/68 (71%) were positive for 5'-NPDase-V, as compared with AFP elevation in 45/68 (66%). 236/268 (88%) cases of cancer with known liver metastases were positive for 5'-NPDase-V. Of 1,040 cancer patients without liver scan or biopsy evidence of metastasis, 316 were positive. In a follow-up of this group of 316 cases, 109 underlying liver metastases were demonstrated by repeat scan or at autopsy within 3--6 months. All 166 sera from normal healthy persons were negative for 5'-NADase-V. Based on this large panel, 5'-NPDase-V test is a sensitive and an important diagnostic aid for cancer patients, both as an early predictor for liver metastases, and a useful marker for primary hepatoma when no other primary sites are found and when there is no evidence of severe chronic liver disease such as cirrhosis.
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PMID:Serum 5'--nucleotide phosphodiesterase isozyme--V test for human liver cancer. 615 48

Incubation of rat hepatoma cells with cAMP derivatives stimulates cell-associated plasminogen activator activity 8- to 22-fold and extracellular plasminogen activator activity 30- to 1300-fold. This time- and concentration-dependent increase is enhanced by phosphodiesterase inhibitors. Dexamethasone, a synthetic glucocorticoid, decreases the plasminogen activator activity of these cells, probably through induction of an inhibitor. Paradoxically, dexamethasone, added simultaneously with cAMP derivatives causes a further 4-fold enhancement of the cAMP-mediated stimulation of plasminogen activator activity. Dexamethasone also alters the time course of cAMP-mediated enhancement of plasminogen activator activity: increased protease activity is detected at 4 hr in cells incubated with 8-bromoadenosine-3':5'-cyclic monophosphoric acid and 1-methyl-3-isobutylxanthine but not until 12 hr in cells incubated with dexamethasone as well. Glucocorticoids thus exert two separate and opposite effects on plasminogen activator activity: induction of an inhibitor and amplification of cyclic nucleotide action. Although permissive and synergistic effects of dexamethasone on cyclic nucleotide action have been reported previously, glucocorticoid regulation of plasminogen activator activity is unique in that the amplification of cyclic nucleotide effects by dexamethasone opposes its regulatory action toward a specific enzyme.
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PMID:Paradoxical effects of glucocorticoids on regulation of plasminogen activator activity of rat hepatoma cells. 617 95

An abnormal, fast-moving 5'-nucleotide phosphodiesterase isozyme was found in 90.0% of 20 Malaysian patients with primary hepatoma and in 23.5% of 391 Malaysian patients with various malignant diseases; it was also discovered in 42.9% of 14 Malaysian and American patients with clinically active hepatitis B infection; in 16.7% of 18 healthy American blood bank donors who were positive for hepatitis B surface antigen (HBsAg); in 13.9% of 287 healthy Malaysian blood bank donors, some positive for HBsAg; and in none of 160 healthy American donors who were negative for HBsAg. A correlation of this abnormal isozyme with hepatoma and with infectious hepatitis B is clearly evident.
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PMID:5'-Nucleotide phosphodiesterase isozyme-V in health, in cancer, and in viral hepatitis. 624 75

Precultured mouse peritoneal macrophages were incubated with a microbial growth inhibitory lymphokine prepared from cell-free ascites of rat Zajdela hepatoma. Cyclic nucleotide metabolism was followed in parallel to experiments demonstrating inhibition of intracellular growth of Corynebacterium murium kutscheri. Maximum increase of cAMP, adenylate cyclase and cAMP-phosphodiesterase activities was found after 60 to 90 min, while inhibition of microbial growth was evident only after 2-3 h. Both effects showed concordant dose dependence. It is concluded that cAMP induces cellular metabolic changes which lead to inhibition of bacterial growth by macrophages.
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PMID:Effect of a microbial growth inhibitory factor on the cyclic nucleotide metabolism of peritoneal macrophages. 626 1

1. Plasma membranes from ascites hepatoma cells (AH-7974, AH-130) contained much smaller amounts of calmodulin (about half) and cyclic AMP phosphodiesterase (about one-third) compared to plasma membranes of rat livers. 2. Some of calmodulin molecules in liver plasma membranes were released by repeated washing. The 'washed' liver plasma membranes showed the presence of specific binding sites for externally added calmodulin molecules (bovine brain) (N = 140 pmol/mg protein, Kd = 7.9 . 10(-8) M). The calmodulin content of AH-7974 plasma membranes was not reduced by repeated washing. The binding of calmodulin to the 'washed' AH-7974 plasma membranes was only of nonspecific nature with negative cooperativity. 3. Plasma membranes (liver and AH-7974) appeared to contain both calmodulin-dependent and calmodulin-independent phosphodiesterase, but the stimulation by externally added Ca2+ plus calmodulin was rather small. Externally added calmodulin-dependent phosphodiesterase (bovine brain) was bound more to 'washed' liver plasma membranes than to 'washed' AH-7974 plasma membranes. Newly bound phosphodiesterase appeared to be more sensitive to the stimulation by Ca2+ plus calmodulin in 'washed' hepatoma plasma membranes than in 'washed' liver plasma membranes. 4. Preincubation of 'washed' plasma membranes (liver and hepatoma) with calmodulin did not affect the binding of phosphodiesterase, but the sensitivity of phosphodiesterase to the stimulation by Ca2+ plus calmodulin in hepatoma plasma membranes was lost.
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PMID:Dynamics of calmodulin and cyclic AMP phosphodiesterase in plasma membranes of rat livers and ascites hepatomas. 627 Dec 50


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