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)

Chronic exposure of H9 cells to 25 microM zidovudine (H9-AZT cells) causes a 2- to 3-fold increase in thymidine kinase (TK) activity (Agarwal RP, Int J Purines Pyrimidine Res, in press). The present study compared thymidine (TdR) and AZT anabolism in H9 and H9-AZT cells. After a 3.5-hr incubation with 10 microM TdR or AZT, the total intracellular accumulations of AZT (48.7 microM in H9 cells and 32.8 microM in H9-AZT cells) were 46.4% of TdR accumulation. Other major differences between TdR and AZT anabolism were: (i) the majority of TdR (84-87%) was incorporated into DNA compared to less than 1% of AZT; and (ii) whereas distribution of TdR in the nucleotides was TTP greater than TMP greater than TDP, zidovudine distributed was AZT-MP much greater than AZT-TP much greater than AZT-DP. Because of the poor substrate activity of AZT-MP for thymidylate kinase (TMP-kinase), most of the AZT (95-98%) remained as AZT-MP. TMP-kinase activities with TMP as substrate were 47.6 +/- 20.3 and 91.4 +/- 28.8 pmol/mg protein/min in H9 and H9-AZT cells, respectively. 5'-Nucleotidase activities with TMP as substrate were 428.9 +/- 37.8 and 255.9 +/- 28.7 pmol/mg protein/min in H9 and H9-AZT cells, respectively. Activities of these enzymes with AZT-MP as a substrate were very low. Despite an increase in TK and TMP-kinase, and a decrease in 5'-nucleotidase activities, the total intracellular accumulations of TdR and AZT were reduced significantly (P less than 0.05) to 67.5% in H9-AZT cells. Thymidine transport (0.66 to 0.68 pmol/sec/10(6) cells) was similar in both the cell lines. The severe reductions of TdR salvage caused by chronic exposure of cells to AZT, if it occurs in AIDS patients on AZT chemotherapy, may explain some of the long-term clinical toxicities of the drug.
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PMID:Thymidine and zidovudine metabolism in chronically zidovudine-exposed cells in vitro. 186 45

Monocrotaline, a pyrrolizidine alkaloid, caused changes in most of the biochemical parameters in rats 12 days after a single dose of 120 mg/kg. These included significantly increased activities of hepatic succinate dehydrogenase, acid ribonuclease, acid phosphatase, gammaglutamyl transpeptidase and 5'-nucleotidase and decreased in the activities of glucose-6-phosphatase and cytochrome P450. The levels of DNA, RNA and glycogen in liver and albumin and protein in serum decreased while serum bilirubin increased. The histopathological changes in liver were characterized by diffused hepatocyte alterations in the form of ballooning, granular cytoplasm, indistinct cell outlines, nuclear changes, focal necrosis, and vascular damage. When picroliv, a standardized iridoid glycoside fraction of Picrorhiza kurroa, was administered orally in a dose of 25 mg/kg simultaneously with monocrotaline, alterations in most of the biochemical parameters along with the histopathological changes in liver caused by monocrotaline were prevented.
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PMID:Picroliv protects against monocrotaline-induced hepatic damage in rats. 190 81

Mature macrophages (Mph) differentiated in culture from normal human peripheral blood monocytes (Mo) exhibit low activity as accessory cells (antigen-presenting cells) in T lymphocyte stimulation. A test system was established based on mitogenicity to quantitate the accessory activity of Mph-derived cells and to follow its changes for several days. The system used accessory cells treated with the oxidative mitogen, sodium periodate. The cells were subsequently co-cultured with pooled human lymphocytes from a cryopreserved stock. DNA synthesis in these cells was used as an indicator of accessory activity. Mph could be converted within 5-6 days into highly active accessory cells if a continuous stimulus of exogenously added dibutyryl cyclic AMP (db-cAMP) was provided. Mph treated by db-cAMP retained a high degree of HLA-DR expression but typical Mph markers such as non-specific esterase, phagocytosis, and expression of Fc-receptors were down-regulated. Acid phosphatase and myeloperoxidase underwent only slight changes, while the monocyte marker 5'-nucleotidase remained undetectable. Morphologically, the cells rounded up and developed veils and dendritiform elongations. In contrast to dendritic cells, Mph-derived accessory cells retained the CD14 antigen characteristic of monocytes and Mph. It is concluded that Mph are able to respond to exogenous stimuli and to convert into a highly active accessory cell. This contrasts to the well-known state of the 'activated Mph' with respect to markers and function. Both states appear to be antagonistically controlled by intracellular second messengers, as the accessory cell phenotype is positively correlated with intracellular cyclic AMP increase, whereas Mph activation correlates with cyclic GMP increase.
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PMID:Accessory phenotype and function of macrophages induced by cyclic adenosine monophosphate. 196 93

Studies were performed on the mode of action of tolnaftate and resistance to this drug in Microsporum gypseum. Cells grown in the presence of tolnaftate (at the IC 50) showed a reduced content of total phospholipids and sterols whereas there was an increase in total RNA content. Incubation of cells with tolnaftate (at 10 x MIC), followed by addition of different macromolecule precursors revealed inhibition of the biosynthesis of all macromolecules except for RNA. The activity of membrane-bound enzymes did not change on treatment with tolnaftate (10 x MIC) whereas an increase in the leakage of intracellular 32P was observed. The content of total phospholipids was higher in tolnaftate-resistant cells, whereas the content of total sterols, DNA, RNA and protein was comparable to that of susceptible cultures. Activity of phosphodiesterase decreased and 5'-nucleotidase increased in tolnaftate-resistant cells. Our results suggest that the antifungal activity of tolnaftate is due to differential action on various targets site(s) which are modified in strains resistant to the drug.
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PMID:Studies on the mode of action of tolnaftate in Microsporum gypseum. 206 94

Thioacetamide (100 mg/kg), when administered to normal rats, caused a significant increase in the activities of 5'-nucleotidase and gamma-glutamyl transpeptidase and a decrease in the activities of glucose 6-phosphatase and succinate dehydrogenase enzymes in the liver. DNA, RNA, and proteins were increased while the cytochrome P450 in the microsomal fraction and the glycogen content in the liver were decreased significantly. Elevations in the activities of GOT, GPT, and alkaline phosphatase and bilirubin content in serum were also observed. Picroliv, a standardised glycoside fraction of Picrorhiza kurroa, in doses of 12.5 and 25 mg/kg prevented most of the biochemical changes induced by thioacetamide in liver and serum. The hepatoprotective activity of Picroliv was comparable with that of silymarin, a known hepatoprotective agent obtained from seeds of Silybum marianum.
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PMID:Picroliv affords protection against thioacetamide-induced hepatic damage in rats. 206 53

Exercise training has been shown to enhance the ability of insulin to stimulate glucose uptake in responsive tissues. The purpose of this study was to determine the effects of exercise training on the levels of the insulin-regulatable glucose transporter (IRGT) in rat skeletal muscle. After 6 wk of voluntary running in exercise-wheel cages, male Sprague-Dawley rats were rested for approximately 27 h and fasted overnight before removal of plantaris and soleus muscles. The concentration of glucose transporters per unit of muscle protein or DNA was quantitated by immunoblotting with an anti-IRGT polyclonal antibody raised against a synthetic peptide. The IRGT protein was increased by 60% (141 +/- 14 vs. 229 +/- 24 counts/min [cpm]/25 micrograms protein, P less than 0.01) in plantaris muscle from exercise-trained rats compared with controls. Total protein yield, DNA content, and 5'-nucleotidase activity were not different in plantaris muscle from control and exercise-trained rats. In contrast, there was no significant increase in the IRGT protein in soleus muscle after training when data were expressed per unit of muscle protein (292 +/- 22 vs. 346 +/- 16 cpm/25 micrograms protein). These data indicate that the increase in the IRGT in plantaris muscle is a selective response to exercise training that does not reflect an overall increase in muscle protein. The changes in IRGT for these muscles with exercise training parallel changes observed in insulin-mediated glucose uptake. We propose that this increase in the total number of glucose transporters may be a major component of the increase in insulin-mediated glucose uptake that is observed with exercise training.
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PMID:Effects of exercise training on insulin-regulatable glucose-transporter protein levels in rat skeletal muscle. 222 15

The purpose of the present investigation was to determine the effect of continuous exposure to the organophosphate monocrotophos at 2.5 ppm for over a period of 2 through 45 days on protein, RNA, and DNA contents and on 5'-nucleotidase activity in the liver of Tilapia mossambica. Protein content was decreased by 45% after 5 days, returned to control levels at 10-30 days, and again decreased by 45 days. DNA content was decreased by 2 days, returned to control values by 5 days, and remained constant throughout the exposure. In contrast, RNA content was significantly lower starting from 2 through 45 days of exposure. 5'-Nucleotidase activity showed a transient increase at 5 and 30 days of monocrotophos exposure. These results indicate that monocrotophos altered the protein, DNA, and RNA contents and the 5'-nucleotidase activity levels as early as 2 and 5 days. However, these changes were reversed by 10 days and after a short period of recovery, the alterations reappeared. This supports our earlier histological observations of hepatic pathology during monocrotophos exposure.
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PMID:Biochemical changes in the liver of fish, Tilapia mossambica (Peters), during continuous exposure to monocrotophos. 245 2

The changes in the biochemical parameters of peritoneal macrophages and their coupling to the secretory and phagocytic functions in CH3A mice during the growth of the reinoculated solid hepatoma 22a were studied. The DNA and RNA synthesis during the active tumour growth was more intense than that in resident macrophages. The activity of uridine kinase increased up to 156.0 +/- 12.0 nmol/hour/10(8) but was absent in resident macrophages. This was accompanied by a 7.2-fold increase of interleukin-1 synthesis as determined by the [3H]thymidine incorporation into thymocyte DNA in response to concanavalin A administration to C3H mice. Similar changes were observed in peptone-stimulated macrophages. A specific feature of macrophages from tumour-bearing mice was the impairment of activity of purine exchange enzymes and the efficiency of phagocytosis that were unobserved in peptone-stimulated macrophages. The activity of adenosine deaminase and purine nucleoside phosphorylase was inhibited as a result of their preincubation with zymosan, a phagocytosis-stimulating agent. This was accompanied by a significant decrease of the first chemiluminescence peak resulting from disturbances in Fc-reception. Macrophages of tumour-bearing animals possessed an increased 2.2-fold activity of membrane-bound AMP 5'-nucleotidase concomitant with the lack or decrease of the amplitude of the second chemiluminescence peak reflecting the disturbances in digestion resulting from phagocytosis.
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PMID:[Change in activity of enzymes for purine metabolism and RNA and DNA biosynthesis in macrophages, reflecting impairment of their functions in neoplastic growth]. 248 7

Two siblings with chronic hemolytic anemia due to red cell pyrimidine-5'-nucleotidase (P-5'-N) deficiency, presented within a few days of each other with a febrile illness and pancytopenia. The cause of the aplastic crisis was an acute infection with human B19 parvovirus (B19 HPV) as proven by immunoelectron microscopy and DNA hybridization. This is the first report on the association of B19-HPV-related aplastic crisis with P-5'-N deficiency.
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PMID:Aplastic crisis due to human B19 parvovirus infection in red cell pyrimidine-5'-nucleotidase deficiency. 254 57

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


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