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)

3':5'-Cyclic-AMP phosphodiesterase (EC 3.1.4.17) and the activating factor of cyclic nucleotide phosphodiesterase were detected in cultured human cell lines from patients with lymphoblastic leukemia and retinoblastoma and in the Brown-Pearce (rabbit) carcinoma. The homogenate of lymphoblasts contained levels of the activating factor in excess of that required to produce maximal activation of the endogenous phosphodiesterase. The activating factor found in these malignant cells appears to be similar to the calcium-binding protein activator of bovine brain phosphodiesterase on the basis of the molecular weight obtained from gel filtration, electrophoretic patterns, calcium requirement for the activity, and the effect of calcium on the proteolysis. In addition, the tumor-derived activator was able to restore the activity of activator-deficient phosphodiesterase from the bovine brain.
J Natl Cancer Inst 1977 Dec
PMID:Cyclic nucleotide phosphodiesterase and protein activator in human cancer cell lines and Brown-Pearce carcinoma. 20 Jul 56

Gentle homogenization followed by differential and density gradient centrifugation was used to purify line 10 and line 1 guinea pig hepatoma plasma membranes in the form of ghosts. Yields of 15--25% allowed enough membranes to be obtained from a single ascites tumor-bearing animal for immunologic and biochemical studies. Although the plasma membrane marker enzyme (Na+ + k+)atpase was present in normal concentrations in both line 10 and line 1 hepatomas, 5'-nucleotidase was reduced over 100-fold in both tumors and phosphodiesterase I was increased 210-fold in the line 10 hepatomas.
J Natl Cancer Inst 1978 Sep
PMID:Preparation of plasma membranes from line 10 and line 1 guinea pig hepatomas. 21 Dec 44

To provide information on the role of nucleases in oncogenic virus infection, the activities of 3'-nucleotide phosphodiesterase (3'-NPDase), 5'-nucleotide phosphodiesterase (5'-NPDase), acid deoxyribonuclease (DNase II), and 3',5'-cyclic AMP phosphodiesterase (cAMPDase) in spleen extracts of murine sarcoma virus-infected C57BL/6 inbred mice were studied. At the peak of tumor growth and of the cell-mediated cytotoxic response (CMC) against tumor-associated antigens, 3'-NPDase, 5'-NPDase, and DNase II all showed depressed activities in the spleen, whereas the activity of cAMPDase in the spleen increased at the peak of CMC and remained elevated thereafter. Serum enzyme activities of the infected mice were also determined, and only 3'-NPD-ase in serum correlated well with CMC. Inasmuch as the correlation of the tumor growth with CMC was established in this system, further study on tumors with variance between CMC and growth is necessary to determine if serum 3'-NPDase is a useful biochemical marker for CMC in vivo.
J Natl Cancer Inst 1978 Oct
PMID:Nucleases and adenosine 3',5'-cyclic monophosphate phosphodiesterase activities in murine sarcoma virus (Moloney)-infected mice. 21 66

A short review of pathogenic factors in U.V. light skin carcinogenesis in the mouse is presented. Caffeine and theophylline applied locally during U.V. irradiation caused a 50 percent reduction of skin tumour induction in Swiss mice. These two chemicals are inhibitors of DNA postreplication repair, but they also raise the intracellular level of cyclic AMP by inhibiting cAMP phosphodiesterase with, as a consequence, a possible slowing down of cellular growth. Control experiments using three different chemicals capable of raising the cAMP level in epidermal cells gave negative results. These experimental data are compatible with our original hypothesis according to which production of skin cancers by U.V. radiation is in same way related to DNA repair which helps the cell to survive but allows or favours the occurrence of errors in cellular DNA.
Bull Cancer 1978
PMID:Ultraviolet light induction of skin carcinoma in the mouse; influence of cAMP modifying agents. 21 89

The potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, produced a 2- to 3-fold increase in the activity of both the low- and high-affinity forms of cyclic adenosine 3':5'-monophosphate phosphodiesterase activity 13 hr after application to mouse skin. The magnitude of the enzyme induction correlated with the tumor-promoting activity of several doses of 12-O-tetradecanoylphorbol-13-acetate and of other phorbol esters. The induction of the low-affinity phosphodiesterase could be blocked by prior i.p. injection of the microtubule poisons, colchicine and vinblastine. The low-affinity cyclic adenosine 3':5'-monophosphate phosphodiesterase activity of the epidermal component of mouse skin papillomas produced by two-stage tumorigenesis was 3 times that of the surrounding uninvolved epidermis.
Cancer Res 1979 Jun
PMID:Increased cyclic adenosine 3':5'-monophosphate phosphodiesterase activity in the epidermis of phorbol ester-treated mouse skin and in papillomas. 22 Oct 99

The effect of different phorbol esters and of mechanical treatment on the activity of ornithine decarboxylase in mouse epidermis in vivo was investigated. The strong promoter 12-O-tetradecanoylphorbol-13-acetate as well as the weak promoters phorbol dibenzoate and the 12-O-tetradecanoylphorbol-13-acetate analog 12-O-tetradeca-2-cis, 4-trans-6,8-tetraenoylphorobol-13-acetate strongly increased the activity of the enzyme and the intraepidermal level of putrescine, with a maximum at 5 hr after application, when applied in doses which evoke comparable proliferative and irritant responses in skin. The hyperplasiogenic but nonirritant and almost nonpromoting 4-O-methyl ether of 12-O-tetradecanoylphorbol-13-acetate did not show such effects. Mechanical removal of the uppermost horny layer led to a considerable increase of ornithine decarboxylase activity after 4 to 8 hr, while skin massage showed only a minute effect under conditions in which both treatments exhibit about the same mitogenic efficiency. Neither manipulation promotes tumor development. After skin massage, the induction of ornithine decarboxylase was influenced neither by treatments which alter the cyclic adenosine 3',5'-monophosphate level in epidermis (inhibition of phosphodiesterase, beta-adrenergic stimulation, and injection of dibutyryl cyclic adenosine 3',5'-monophosphate) nor by injection of epidermal G1 chalone. The results indicate that no clear-cut correlation exists between epithelial cell proliferation, development of hyperplasia, and tumor promotion on the one hand and an activation of epidermal ornithine decarboxylase on the other.
Cancer Res 1979 Oct
PMID:Ornithine decarboxylase activity, cell proliferation, and tumor promotion in mouse epidermis in vivo. 22 17

The antitumour agent 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) was found to inhibit competitively the low-Km cyclic AMP phosphodiesterase activity in an ammonium-sulphate-precipitable fraction of the 2,000g supernatant of rat liver. With substrate concentration at 0.25 microM, I50 was 790 microM for DTIC and 350 microM for theophylline. DTIC at 2 mM more than doubled the cAMP response to glucagon in hepatocytes and to adrenaline in MH1C1 hepatoma cells, indicating that it also exerts its inhibitory effect on the phosphodiesterase in intact cells. The possible contribution of the phosphodiesterase inhibition to the growth-inhibitory and cytotoxic effects of DTIC is discussed.
Br J Cancer 1979 Nov
PMID:The antitumour agent 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC) inhibits rat liver cAMP phosphodiesterase and amplifies hormone effects in hepatocytes and hepatoma cells. 22 92

The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in 1,2-dimethylhydrazine (DMH) induced rat colon tumors were previously reported to be one-half and twice, respectively, that measured in normal rat colon tissue. The results of this present study indicate that the total amount of cyclic nucleotide hydrolysis by the phosphodiesterase enzymes (PDE) could account for the lower cAMP and elevated cGMP noted in cancer tissue. PDE activities in homogenates prepared from normal and neoplastic tissue showed general similarities in both their hydrogen and metal ion dependencies with optimum degradation of nucleotides occurring at pH 7.2-7.8 in the presence of either Mg2+ or Mn2+ ions. The enzymes from both tissue types were inhibited to a similar extent by papaverine and theophylline. Distribution studies indicated PDE activities were similar throughout the entire length of the normal colon; consequently, the anomalous activities measured in the tumors were attributable to the specific cell population and not to the particular site at which malignancy arose. Thus, the findings of this study suggest that one cause for lowered cAMP and elevated cGMP levels in DMH induced colon adenocarcinomas was the amount of cyclic nucleotide hydrolysis by PDE in the malignant tissue.
Cancer Lett 1979 Aug
PMID:Adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate phosphodiesterase activities in 1,2-dimethylhydrazine induced colon adenocarcinoma. 22 47

Cyclic nucleotide phosphodiesterase activity has been measured in muscle biopsies taken from healthy controls and from cancer patients. In both groups the muscles were clinically and morphologically normal. The phosphodiesterase activity was significantly increased in muscles from cancer patients using both cyclic AMP and cyclic GMP as substrate. These findings are in line with previous reports indicating that malignancy may interfere with metabolism of the host muscular tissues, and suggest the possibility that the observed biochemical changes might be an aspect of an early muscle neurogenic involvement.
 ...
PMID:Cyclic nucleotide phosphodiesterase activity in muscle of patients with carcinoma. 23 Mar 21

Serum phosphodiesterase I (PDE I) activity was determined in 13 control and 51 breast-cancer patients with various stages of disease. Patients with both localized and metastatic breast cancer had significantly elevated serum PDE I activity. The highest activity was seen in patients with liver metastases. A decline in serum PDE I activity was seen after surgical resection of all known disease.
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PMID:Serum phosphodiesterase I activity in breast cancer patients. 23 44


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