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)

Adenosine deaminase (ADA) and 5'-nucleotidase (5'-N) activity and cytotoxic activity (CTA) of natural killer cells (NK-cells) isolated from human peripheral blood were studied. These cells were affected by culture medium obtained after the contact of tumour cells with NK-cells, the degree of malignancy in these cells being different. It has been established that pretreatment of NK-cells with culture medium from highly malignant cells and containing PGE, causes a sharp inhibition of their CTA, which is accompanied by an essential decrease of the ADA activity and an increase of the 5'-N activity in these cells as compared with the control.
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PMID:[Effect of the prostaglandin E produced by tumor cells on the enzymatic activity of adenosine metabolism and on human natural killer cytotoxic activity]. 254 31

Previous studies reported that 5'-nucleotidase activity was undetectable or at much lower levels in the homogenate of human chronic lymphocytic leukemic (CCL) cells than in normal lymphocytes. In the present study, 5'-nucleotidase specific activity in acute myelocytic leukemia (AML), which varied in a range from undetectable to 1.4 (nmoles/min.mg protein), was enhanced by cell fractionation, from undetectable in the homogenate, up to 18.8 +/- 1.2, 6.4 +/- 0.7 and 0.68 +/- 0.12 in plasma membranes, microsomes, and cytosol fraction, respectively. In a further fractionation of the cytosol of various leukemic cells with ammonium sulfate, 5'-nucleotidase specific activity increased up to 14-fold in the 60% (NH4)2SO4 fraction, with a recovery of 1266 +/- 115%. These data suggest that 5'-nucleotidase activity in fractionated leukemic cells is higher than reported previously and that the sum of 5'-nucleotidase activity in subcellular compartments is higher than that detected in the homogenate. Furthermore, even when 5'-nucleotidase was undetectable in a homogenate, it became detectable in the plasma membranes, suggesting that its ecto-enzyme function is still active in leukemic cells. The undetectable or low 5'-nucleotidase in the homogenate is indicative of (1) the enzyme itself being in an inactive form but becoming active after the fractionations, or (2) the presence of a factor(s) that prevents the enzyme from being detected but that is separated from the enzyme by the fractionations. In both cases, the rate of nucleotide catabolism by inactive 5'-nucleotidase in rapidly proliferating leukemic cells should be slower than when the enzyme is active. The present finding is consistent with our previous findings that during normal cell aging the high 5'-nucleotidase activity is associated with senescent non-proliferating cells but low or undetectable activity with rapidly proliferating immortal cells. The implications of 5'-nucleotidase for DNA synthesis in aging and cancer are discussed.
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PMID:Enhancement of 5'-nucleotidase activity of human leukemic cells after fractionation: implications for cancer and aging. 255 27

Damage to the vasculature may represent an important component of several forms of cancer therapy. Methods for studying the structure and function of the vasculature of experimental mouse tumours are required. In this paper several relatively simple methods are described for the histological examination of the vascular structure of murine tumours. The methods have been applied to cryostat sections of two sarcomas and two carcinomas. Immunoperoxidase staining with polyclonal antibodies to laminin highlights the vascular basement membrane of sarcomas, but has limited use with carcinomas, while the monoclonal antibody MECA-20 is a good marker for the endothelial cells of all vessels in all four tumours tested. The presence of endothelial cells in normal tissues can also be demonstrated by the use of enzyme-histochemical techniques for alkaline phosphatase, 5'-nucleotidase and nucleotide diphosphatase (ADPase), but only one of these methods (ADPase) works consistently in tumours. The relative merits of these methods are discussed and in all cases related to the staining pattern obtained with normal mouse tissues. The significance of these methods for vascular targeting is also discussed.
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PMID:Vascular markers for murine tumours. 268 20

We have previously reported that 5'-aminothymidine (5'-AdThd), an antagonist of the feedback inhibition exerted by dTTP that regulates thymidine kinase, enhances the uptake and cytotoxicity of 5-iododeoxyuridine in various human bladder cancer cell lines but not in normal human urothelial cells (HU) propagated in vitro. In this work we have analyzed the factors that could potentially account for the differential effect of 5'-AdThd among various cell types: 647V (a human bladder cancer cell line); HU; SV-HU (a SV40-transformed human urothelial cell line), and C3H/10T1/2 mouse embryo fibroblasts (10T1/2) cells. 5'-AdThd enhanced the uptake of IdUrd in SV-HU cells (greater than 400%), similar to what we have observed before for 647V cells. However, in 10T1/2 and HU cells, 5'-AdThd only minimally increased the uptake of 5-iododeoxyuridine (about 160%). Thymidine kinases purified from the different sources were similarly sensitive to inhibition by dTTP or 5'-AdThd and to deinhibition of the dTTP-induced regulation of enzyme activity by 5'-AdThd. Furthermore, [3H]-5'-AdThd permeated and accumulated intracellularly in all cell types. In none of these cultures was nucleoside phosphorylase activity detected, as indicated by the inability of the cells to produce thymine or iodouracil after exposure to the appropriate nucleosides. Also, 5'-AdThd did not affect the breakdown of dTMP by crude preparations of cytosolic 5'-nucleotidase from the different cells. We found that intracellular dTTP pools in the various cell types were substantially high (15-26 microM) compared to the sensitivity of thymidine kinase to inhibition by dTTP (IC50 2-4 microM). This suggests that thymidine kinase is in a strongly inhibited state in situ. To test the sensitivity of thymidine kinase (in situ) to regulation by dTTP we investigated: (a) the effect of depleting intracellular dTTP pools with methotrexate on the uptake of thymidine (dThd); and (b) the effect of pH on the uptake of dThd and its perturbation by 5'-AdThd, since the inhibition of thymidine kinase activity by dTTP is known to be pH dependent. We found that a 47% reduction of dTTP pools by methotrexate in 10T1/2 and HU cells did not result in an increase in thymidine kinase activity, as indicated by the lack of an effect on the uptake of dThd. However, we have previously shown that, under similar conditions, 647V cells show a substantial increase in dThd uptake.(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Res 1989 May 01
PMID:Basis for the differential modulation of the uptake of 5-iododeoxyuridine by 5'-aminothymidine among various cell types. 270 29

The sensitivity to photodynamic treatment of three plasma membrane enzymes in R3230AC mammary adenocarcinomas was assessed. The activities of Na+K+-ATPase, Mg2+-ATPase and 5'-nucleotidase in isolated membranes were measured after exposure of membranes to either hematoporphyrin derivative or Photofrin II plus light in vitro or in tumor membranes prepared from animals previously injected with 25 mg/kg Photofrin II and sacrificed at various times prior to exposure to light (in vivo-in vitro protocol). The activities of both Na+K+-ATPase and Mg2+-ATPase were inhibited at equivalent rates by Photofrin II in vitro; inhibition was drug dose and light dose related. For 5'-nucleotidase in vitro, a 10-fold higher porphyrin concentration was required to achieve a similar rate of enzyme inhibition as that for the ion-activated ATPases. Injection of Photofrin II in vivo followed by preparation of tumor plasma membranes, which were subsequently exposed to light in vitro, produced no photosensitization of 5'-nucleotidase activity at any time studied (up to 72 h after Photofrin II administration). Under the same conditions Na+K+-ATPase activity was reduced by 40-60% from 2 to 72 h after drug injection, whereas Mg2+-ATPase activity was inhibited by 10-25% over the same time course. The differential sensitivity of these three enzymes observed in this in vivo-in vitro protocol suggests that each enzyme may possess different characteristics, such as three-dimensional configuration or membrane location, that afford varying susceptibility to porphyrin photosensitization. The data also suggest that photosensitivity-induced damage to these ion-activated plasma membrane ATPases could have deleterious effects on tumor cell survival.
Cancer Res 1988 Jun 15
PMID:Photosensitizing effects of hematoporphyrin derivative and photofrin II on the plasma membrane enzymes 5'-nucleotidase, Na+K+-ATPase, and Mg2+-ATPase in R3230AC mammary adenocarcinomas. 283 53

DU-PAN-2 is a high-molecular-weight glycoprotein defined by a murine monoclonal antibody (MAb) elicited against a human pancreatic adenocarcinoma cell line. This MAb recognizes an oncofetal antigen present on the surface of normal pancreatic and bile-duct epithelium, normal bronchus epithelium, and some adenocarcinomas. Elevated levels of the antigen (greater than 400 U/ml) have been detected in the serum of 79% of patients with adenocarcinoma of the pancreas and in a small percentage of patients with other adenocarcinomas, by means of a competition radioimmunoassay. Here, we have studied DU-PAN-2 antigen levels in sera of patients with a spectrum of hepatobiliary diseases and controls. Serum DU-PAN-2 antigen was elevated in 59% of 112 patients with non-malignant hepatobiliary diseases and in 50% of hepatoma patients. None of 50 healthy controls had elevated serum DU-PAN-2 levels. Patients in every category of hepatobiliary disease studied had elevated median serum DU-PAN-2 levels; the highest median levels were seen in patients with primary biliary cirrhosis (1,296 U/ml) and the lowest in stable cirrhosis (300 U/ml). Elevated serum DU-PAN-2 levels in one patient with primary biliary cirrhosis and in one patient with hepatoma returned to normal following liver transplantation. Serum DU-PAN-2 levels did not correlate well with alkaline phosphatase, 5'-nucleotidase, bilirubin, or alpha-fetoprotein. Using an immunoperoxidase technique on formalin-fixed, deparaffinized liver sections, we showed that DU-PAN-2 MAb reacted heterogeneously with bile-duct epithelium but never stained hepatocytes or hepatoma cells. While serum DU-PAN-2 levels may be useful in detecting and monitoring pancreatic adenocarcinoma, they are not specific for this disease.
Int J Cancer 1988 Jun 15
PMID:Detection of an oncofetal antigen (DU-PAN-2) in sera of patients with non-malignant hepatobiliary diseases and hepatomas. 283 18

The metabolism of 6-mercaptopurine (6-MP) in L-1210 mouse leukemia cells and human chronic myelocytic leukemia cells (CML cells) was examined. The acid-soluble fractions obtained from cells incubated with [8-14C]6-MP were chromatographed on a Dowex-1 formate resin column using a formic acid linear gradient elution system. Chromatography of the extract of L-1210 cells revealed four principal radioactive peaks. The fraction containing the third peak was hydrolyzed by snake venom 5'-nucleotidase (Crotalus adamanteus). Cellulose thin layer chromatography revealed that the radioactive peak of the hydrolysate corresponded to 6-thioguanosine. The results showed that 6-MP was converted to 6-thioinosinic acid (6-TIMP) and 6-thioguanylic acid (6-TGMP) in L-1210 cells. In order to elucidate the pathway of 6-MP conversion to 6-TGMP, we examined the interaction of [8-14C]6-TIMP and purified IMP dehydrogenase. It was found by DEAE-cellulose thin layer chromatography that the IMP dehydrogenase converted 6-TIMP to 6-thioxanthylic acid (6-TXMP). Dowex-1 chromatography of the acid-soluble extract of human CML cells incubated with [8-14C]-6-MP also revealed a radioactive peak corresponding to 6-TGMP. These results suggest that 6-MP is metabolized to 6-TGMP by serial conversion to 6-TIMP and 6-TXMP through the de novo GMP synthetic pathway in L-1210 cells and human CML cells.
Jpn J Cancer Res 1985 Feb
PMID:Conversion of 6-mercaptopurine to 6-thioguanylic acid in L-1210 cells and human leukemia cells. 285 24

The human monocytic leukemia cell line, THP-1, is induced to differentiate into more functionally mature monocyte (macrophage)-like cells by incubation with retinoic acid at concentrations of 10nM or higher. There is no apparent morphological change accompanying this functional maturation. These induced cells show increases in nitroblue tetrazolium reduction, immunoerythrophagocytosis, hexose monophosphate shunt activity, and 5'-nucleotidase and NAD+-glycohydrolase activities. Prostaglandin E2, dibutyryl cyclic adenosine 3':5'-monophosphate, or T-lymphocyte-derived differentiation-inducing activity, all inactive or less active alone, increase the extent of differentiation of THP-1 in combination with 10nM retinoic acid. THP-1 is also induced to differentiate by 0.1nM or higher concentrations of cholera toxin. Furthermore, 24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 induces less differentiation of THP-1 compared to retinoic acid. Dimethyl sulfoxide and 12-O-tetradecanoylphorbol-13-acetate show no induction of functional differentiation. THP-1 thus joins the list of leukemic myelomonocytic cell lines (e.g., the promyelocytic HL-60 and the monoblast-like U-937) that are blocked at a relatively late stage of maturation and which differentiate in response to retinoic acid.
Jpn J Cancer Res 1985 May
PMID:Induction of functional differentiation of a human monocytic leukemia cell line (THP-1) by retinoic acid and cholera toxin. 298 63

Galactosyltransferase (GalTF), sialyltransferase (SiaTF), fucosyltransferase (FucTF), 5'-nucleotidase (5'Nucl), and ADP-ribosyltransferase (RibTF) were determined in three subcellular fractions of tumor cells and adjacent control tissue from 20 patients with small primary infiltrating ductal adenocarcinomas of the breast. Viable, as pure tumor cell populations as possible were isolated, subfractionated, and their enzyme levels compared to those in the patients' sera. The activities in tumor cells of the three glycosyltransferases were two- to seven-fold higher, whereas 5'-Nucl and RibTF showed reduced activities when compared to adjacent noninvolved tissue. Serum GalTF and SiaTF were slightly elevated in early mammary carcinoma, whereas FucTF, 5'Nucl, and RibTF were decreased in comparison with a control group. The proposed tumor origin of circulating enzymes could not be confirmed. Surprisingly, only for RibTF could a correlation between tumor and serum activity be established; a weak correlation was found for SiaTF. However, no such relationship could be determined for GalTF, FucTF, or 5'Nucl. In conclusion, the enzyme profile of the tumor cell does not, except for RibTF, appear in the serum. Serum enzyme profiles, therefore, do not permit detection of the early stages of breast cancer. A high correlation between RibTF activity and cytosol estrogen and progesterone receptor levels has been determined in tumor cells, possibly indicating slower growing, more differentiated types of breast tumors.
Cancer Detect Prev 1985
PMID:Enzyme activities in human breast tumor cells and sera. 299 19

The exact route of metabolism of tiazofurin, a novel nucleoside with antitumor activity, is controversial. Using human cell lines severely deficient in salvage nucleotide enzymes, we were able to identify the route of activation in tiazofurin metabolism. With loss of adenosine kinase activity by mutation in two lymphoblastoid cell lines, CCRF-CEM and WI-L2, the growth sensitivity to tiazofurin decreased by 6- and 3-fold, respectively. In contrast, the mutant lines were about 3000- to 1500- and 16- to 4-fold more resistant to the structurally similar tiazofurin analogues pyrazofurin and ribavirin, respectively. Other mutants with defective deoxycytidine or uridine kinase activity showed normal sensitivity to all three analogues. Both cell lines with defective adenosine kinase activity accumulated about 50% wild-type levels of tiazofurin-5'-monophosphate and thiazole-4-carboxamide adenine dinucleotide analogue of tiazofurin at cytotoxic concentrations of the drug. Extracts of wild-type lymphoblasts catalyzed the phosphorylation of tiazofurin in the presence of adenosine 5'-triphosphate and Mg2+. Loss of adenosine kinase activity in the mutant extract eliminated this phosphorylating activity for tiazofurin consistent with the notion that adenosine kinase catalyzes phosphorylation of tiazofurin. However, an enzyme activity that catalyzed the phosphorylation of tiazofurin in the presence of inosine-5'-monophosphate as donor and Mg2+ was detected in the extracts of both wild-type cells and adenosine kinase-deficient mutants. The monophosphate donor specificity, divalent metal, high salt requirement, and nucleoside acceptor specificity of this enzyme activity paralleled that of a 5'-nucleotidase (EC 3.1.3.5) which catalyzes inosine phosphorylation. In addition, tiazofurin phosphorylation was competitively inhibited by inosine and the apparent Ki value was similar to the apparent Km value for inosine phosphorylation. These results indicate that two enzymes, adenosine kinase and a cytoplasmic 5'-nucleotidase, are functionally important anabolizing enzymes for tiazofurin in human cells.
Cancer Res 1986 Feb
PMID:Tiazofurin metabolism in human lymphoblastoid cells: evidence for phosphorylation by adenosine kinase and 5'-nucleotidase. 300 May 75


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