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)

Changes in levels of purine degradative enzymes have been shown to occur during T-cell maturation in both rats and humans with a fall in adenosine deaminase (ADA) and a rise in purine nucleoside phosphorylase (PNP) and 5'-nucleotidase (5'NT) activities. We have investigated the effects of four thymic factors: thymosin fraction 5 (TMS-F5); thymosin alpha 1 (TMS-alpha 1); thymopoietin pentapeptide (TP-5); and thymic conditioned medium (CM) on TdT activity, purine enzyme levels and the phenotypic markers OKT3 (a marker for mature T cells) and NA1/34 (which reacts with immature cortical thymocytes) in human thymocytes and in the lymphoid leukaemic cell lines RPMI-8402 and JM1 (derived from Thy-ALL). All four thymic factors caused one or more maturation change in human thymocytes, e.g. TMS-F5 caused a significant increase in OKT3 expression, TMS-alpha 1 a fall in TdT and ADA activities and a rise in OKT3-positive cells, TP-5 an increase in PNP and CM a rise in 5'NT activity. TMS-F5 also caused a marked elevation of 5'NT in both the T lymphoblastic lines (P less than 0.001). On the other hand the non-physiological phorbol ester, 12-O-tetradecanoyl phorbol acetate (TPA), a tumour promotor with potency of inducing differentiation in some leukaemic cell lines, induced changes in both normal thymocytes and in the leukaemic line JM1 were inconsistent with maturation, e.g. a fall in the percentage of OKT3 cells. These observations suggest that maturation of normal thymocytes might proceed stepwise, each step requiring at least one of the thymic hormones. Although thymosin also induces differentiation changes in a malignant lymphoid line, the pattern of these differs from that induced in their normal counterparts.
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PMID:Biochemical and immunological differentiation of human thymocytes induced by thymic hormones. 660 5

Plasma membranes were isolated from lymphoid cells of benign thymomas obtained from inbred BUF/Mna rats (21 mo old) and from normal thymocytes obtained from young rats (7 wk old) of the same strain. The isolated plasma membranes were electron microscopically pure, and the specific activities of Na+, K+-ATPase, and 5'-nucleotidase were enhanced. The lipid compositions of the plasma membranes from these two sources were analyzed and compared. The cholesterol and plasmalogen contents of membranes from both sources were similar, but the phospholipid content of the benign thymoma lymphoid cell membranes was slightly lower than that of the normal thymocytes, resulting in a somewhat higher molar ratio of cholesterol to phospholipid. The plasma membranes of the thymoma lymphoid cells also exhibited a slightly higher microviscosity as measured with fluorescence polarization. No significant differences were observed in the phospholipid compositions of the two membrane preparations.
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PMID:Lipid analysis of isolated plasma membranes of lymphoid cells in benign thymomas of Buffalo/Mna rats. 693 30

A rapid isolation method was developed for plasma membranes from mouse lymphoid cells such as lymph node lymphocytes, thymocytes, radiation-induced thymoma cells and L1210 cells. Lysates of these lymphoid cells were prepared by Dounce homogenization under hypotonic conditions and directly layered on sucrose step density gradients containing 2 mM CaCl2 and 5 mM MgCl2, and centrifuged at 52 000 X g for 1 h. Plasma membrane fractions appeared at the interface between 20 and 42% sucrose in the gradients. The procedure permitted purified membranes from cells to be obtained within 3 h, and the preparations appeared to be uniform by electron microscopy. Specific activities of (Na+ + K+)-ATPase, Mg2+-ATPase and 5'-nucleotidase of the isolated plasma membranes were enriched 23- to 61-fold, 12- to 15-fold and 18- to 34-fold, respectively, in comparison with those of the corresponding cell homogenates. Cholesterol content of the malignant cell membranes was lower than that of the normal membranes and the molar ratio of cholesterol to phospholipid of the malignant cell membranes was also lower than that of the normal membranes. A decreased plasmalogen content was observed in the malignant plasma membranes, together with a higher percentage of phosphatidylethanolamine and a lower percentage of phosphatidylserine. In the normal cell membranes, thymocytes contained a higher percentage of phosphatidylcholine and a lower percentage of sphingomyelin than those of the lymph node lymphocytes. At all temperature ranges (5 to 40 degrees C) the plasma membranes of the malignant cells had lower microviscosity than those of the normal cells.
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PMID:Rapid isolation and lipid characterization of plasma membranes from normal and malignant lymphoid cells of mouse. 731 6

The nucleoside analog 2-chlorodeoxyadenosine (CdA, Cladribine) is a chemotherapeutic agent for treatment of leukemias and lymphomas, most successfully used in hairy cell leukemia and B-cell chronic lymphocytic leukemia. CdA is phosphorylated intracellularly to its monophosphate derivative by the enzymes deoxycytidine kinase and deoxyguanosine kinase. Cell lines deficient in deoxycytidine kinase were shown to be resistant to CdA and a high deoxycytidine kinase level in combination with low 5'-nucleotidase has been proposed to partly explain the selectivity in CdA toxicity for lymphoid cells. In this report biochemical properties in CdA phosphorylation mediated by deoxycytidine kinase and deoxyguanosine kinase are reviewed and discussed in relation to the further metabolism of CdA 5'-monophosphate, the different possible mechanisms of action and the correlation with clinical response. It is concluded that much is known about the metabolism and mechanisms of action of CdA, but that the remarkable therapeutic effect in hairy cell leukemia has yet to be explicitly explained.
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PMID:On the phosphorylation of 2-chlorodeoxyadenosine (CdA) and its correlation with clinical response in leukemia treatment. 872 3

Adenosine has potent immunosuppressive activity. Since the source of adenosine and the mechanism of its release in the immune system is largely unknown and may vary according to cell type, we have evaluated the relationship between adenosine metabolism and the enzymatic activities and mRNA levels of adenosine-metabolizing enzymes in myeloid and lymphoid cell lines. Induction of HL-60 cell differentiation along the macrophage lineage by PMA resulted in a reduction in the activities of adenosine deaminase (ADA), adenosine kinase (AK), and inosine monophosphate-specific cytosolic 5'-nucleotidase and an elevation of ecto-5'-nucleotidase (ecto-5'-NT). These changes were accompanied by an elevation of ecto-5'-NT mRNA and a decrease in ADA and AK mRNAs in a time-dependent fashion. Comparison of AK and ADA mRNA levels in several other leukemic cell lines revealed generally similar responses to PMA with much stronger suppression in immature T cells than in B cells. The metabolism of adenosine either through phosphorylation (AK) or deamination (ADA) was reduced in PMA-stimulated cells. Furthermore, the cumulative changes in enzyme expression resulted in a 2.5-fold increase in intracellular adenosine formation in PMA-stimulated cells. The inhibition of AK by 5'-iodotubercidin further increased adenosine formation by 6-fold over that in untreated cells. In accord with the increase in ecto-5'-NT activity, extracellular AMP dephosphorylation increased dramatically, but there was no increase in extracellular ATP degradation. These results indicate that a coordinated shift in adenosine-metabolizing enzyme levels during PMA-induced HL-60 cell differentiation is accompanied by a decrease in adenosine uptake and an increase in adenosine release.
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PMID:Adenosine metabolism during phorbol myristate acetate-mediated induction of HL-60 cell differentiation: changes in expression pattern of adenosine kinase, adenosine deaminase, and 5'-nucleotidase. 914 13

The metabolism of purine nucleotides was studied in human peripheral blood lymphocytes from healthy subjects and patients with B-cell chronic lymphocytic leukemia. Nucleotide content was determined by HPLC. The rate of de novo synthesis of purine nucleotides was measured kinetically by following the incorporation of 14C-formate into the nucleotides of a lymphocyte suspension. The patterns of the main enzymes involved in purine nucleotide metabolism (those of the salvage pathway and catabolism) were estimated by a radiochemical method. Although the data expressed in relation to cells and protein showed some discrepancies, several common differences were evident in both cases. The main differences were an increase in NAD and IMP, a sharp decrease in 5'-nucleotidase activities and in total guanylate content and synthesis, and an increase in the A/G ratio in lymphocytes of patients with respect to controls. The changes in these parameters in CLL indicate an imbalance in purine metabolism and may play a specific role in the biology of the leukemia cell. They are also potential biochemical markers of lymphoid malignancies and may be useful in chemotherapic applications.
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PMID:Purine nucleotide metabolism: specific aspects in chronic lymphocytic leukemia lymphocytes. 919 62

The histochemical localisation of two ecto-enzymes, 5'-nucleotidase (5'-NT) and Mg(2+)-ATPase, was investigated in hyperplastic and recurrent tonsillitis. Detection of enzymes was performed on frozen sections using the classical lead nitrate method. Activity of 5'-NT was demonstrated particularly in the cells of lymphoid follicles and in the basal layer of the surface tonsillar epithelium. There was no difference in localisation of 5'-NT between hyperplastic and recurrent tonsillitis, whereas a stronger reaction in follicular mantle zones was observed in recurrent tonsillitis compared to hyperplastic tonsillitis. Mg(2+)-ATPase activity was mainly associated with the cells lining the tonsillar crypt, with the interfollicular areas and blood vessels. In recurrent tonsillitis only half of the studied follicular germinal centres expressed Mg(2+)-ATPase activity, compared to hyperplastic tonsillitis. The similar localisation of 5'-NT and ecto-ATPase in both types of chronic tonsillitis suggests that in inflamed tonsils expression of investigated enzymes probably does not depend on the type of chronic tonsillitis.
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PMID:Localisation of ecto-5'-nucleotidase and divalent cation-activated ecto-ATPase in chronic tonsillitis. 957 64

Many enzymes are involved in the biosynthesis, interconversion, and degradation of purine compounds. The exact function of these enzymes is still unknown, but they seem to play important roles other than in purine metabolism. To elucidate their functional roles, it is imperative to clarify their tissue distribution at the cellular or subcellular level. The present review summarizes the currently available information about their histochemical localization and proposed functions. In general, 5'-nucleotidase has been considered as a marker enzyme for the plasma membrane, and is considered to be a key enzyme in the generation of adenosine, a potential vasodilator. However, from its wide range of localization in tissues it is also considered to be related to the membrane movement of cells in the transitional epithelium, cellular motile response, transport process, cellular growth, synthesis of fibrous protein and calcification, lymphocyte activation, neurotransmission, and oxygen sensing mechanism. Adenosine deaminase (ADA) is present in all tissues in mammals. Although the main function of ADA is the development of the immune system in humans, it seems to be associated with the differentiation of epithelial cells and monocytes, neurotransmission, and maintenance of gestation. Purine nucleoside phosphorylase (PNP) is generally considered as a cytosolic enzyme, but recently, mitochondrial PNP, a different protein from cytosolic PNP, was reported. PNP is also widely expressed in human tissues. It is found in most tissues of the body, but the highest activity is in peripheral blood granulocyte and lymphoid tissues. It is also related to the development of T-cell immunity in humans as is ADA. Moreover, its contribution to centriole replication and/or regulation of microtubule assembly has been suggested. Immunohistochemical localization of xanthine oxidase has been reported in various tissues from various animal species. Xanthine oxidase has been suggested to be involved in the pathogenesis of post-ischemic reperfusion tissue injury through the generation of reactive oxygen species, while the extensive tissue localization of xanthine dehydrogenase/oxidase suggests several other roles for this enzyme, including a protective barrier against bacterial infection by producing either superoxide radicals or uric acid. Furthermore, an involvement in cellular proliferation and differentiation has been suggested. Urate oxidase is generally considered a liver-specific enzyme, except for bovines which possess this enzyme in the kidney. Urate oxidase is exclusively located in the peroxisomes of fish, frogs, and rats, but was lost in birds, some reptiles, and primates during evolution. A histochemical demonstration of allantoin-degrading enzymes has not been performed, but these enzymes have been located in peroxisomes by sucrose density gradient centrifugation. AMP deaminase activity is higher in skeletal muscle than in any other tissues. AMP deaminase may be involved in a number of physiological processes, such as the conversion of adenine nucleotide to inosine or guanine nucleotide, stabilizing the adenylate energy charge, and the reaction of the purine nucleotide cycle. There are three distinct isozymes (A, B, C) with different kinetic, physical, and immunological properties. Isozymes A, B, C have been isolated from muscle, liver (kidney), and heart tissue, respectively. In the muscle, AMP deaminase isozymes exist in a different part, suggesting a multiple functional role of this enzyme. High hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity is found in some regions of a normal adult human brain. However, very little is known regarding the histochemical tissue localization of HGPRT. Immunohistochemical localization of its developmental expression suggests that HGPRT may not be essential for purine nucleotide supplement in the segmentation of brain cells, but may play a significant role in the developing hippocampus.
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PMID:Enzymes involved in purine metabolism--a review of histochemical localization and functional implications. 1050 47

The present study has investigated the relationship between pancreatic lymphatics, infiltrating cells, and insulitic development after a single injection of complete Freund's adjuvant (CFA) given at an early age in the nonobese diabetic (NOD) mice. No CFA-treated NOD mice developed hyperglycemia, whereas most CFA-untreated mice died of diabetes at the age of 20-30 weeks. In untreated NOD mice, the increased infiltration of dendritic cells (DCs) and T-lymphocytes into the pancreatic islets appeared to be consistent with the increased expression of the secondary lymphoid chemokine (CCL21) and CD(31) by the endothelial cell lining of inter- and intralobular lymphatics. As the infiltration became severe, the reaction products of CCL21 and CD(31) were distributed in the nucleus and cytoplasm of lymphatic endothelial cells (LECs), through which DCs and T-lymphocytes migrated frequently. Administration of CFA reduced the number of infiltrating DCs and T-lymphocytes, but did not affect macrophage infiltration. The peri-insulitis occurred in numerous islets of CFA-treated NOD mice without the appearance of the intraislet infiltration and islet-associated lymphoid-like tissues. Furthermore, significant suppression of CCL21 and CD(31) was demonstrated on the infiltrating cells to the islets and islet-associated lymphatics. The abluminal endothelial cell lining of lymphatic vessels exhibited weaker immunoreactivity of CCL21 and CD(31) in comparison with the luminal surfaces. The reaction product of 5'-nucleotidase (5'-Nase) was evenly deposited on LECs, which were the absence of open junctions, cytoplasmic protrusions, and vesicles. CFA treatment influenced the migratory processes of the infiltrating cell, which were closely related with structural changes of pancreatic lymphatics and inhibited insulitic development. These findings suggest that in CFA-treated NOD mice, the suppression of insulitis and prevention of diabetes are secondary to the functional modulation of pancreatic lymphatics and infiltrating cells.
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PMID:Study on pancreatic lymphatics in nonobese diabetic mouse with prevention of insulitis and diabetes by adjuvant immunotherapy. 1538 76

Gemcitabine is an inhibitor of ribonucleotide reductase (RR) and DNA polymerization with promising activity in hematologic malignancies. Gemcitabine enters the cell mostly via the human equilibrative nucleoside transporter-1 (hENT1), while drug metabolism occurs by phosphorylation by deoxycytidine kinase (dCK), 5'-nucleotidase (cN-II) and cytidine deaminase (CDA) are the main inactivating enzymes. The aim of this study was to investigate the role of these determinants in gemcitabine cytotoxicity and analyze their expression in lymphoid cells. Cytotoxicity was assessed by MTT, and modulated by simultaneous addition of 2'-deoxycytidine (dCK natural substrate), tetrahydrouridine (CDA competitive inhibitor) and diethylpyrocarbonate (cN-II non-competitive inhibitor), while the expression of hENT1, dCK, cN-II, CDA and RR in WIL2-S, Jurkat and CCRF-CEM cells as well as in lymphoid cells from 25 chronic lymphocytic B-leukemia (B-CLL) patients was studied with quantitative-PCR. Cell cycle modulation and induction of apoptosis were analyzed by cytofluorimetry and bisbenzimide staining. Gemcitabine was highly cytotoxic, increased the cells in S-phase and significantly enhanced apoptosis. The crucial role of metabolism in gemcitabine activity was confirmed by the significant modulation of cytotoxicity by inhibitors of dCK, CDA and cN-II. Furthermore, PCR demonstrated a correlation between gemcitabine sensitivity and expression of its determinants, and that their values were within those observed in patients. These data indicate that gemcitabine is cytotoxic against lymphoid cells, affecting cell cycle and apoptosis. Furthermore, chemosensitivity may be predicted on the basis of gene expression profile of critical determinants involved in gemcitabine mechanism of action, suggesting the use of pharmacogenetic profiling for treatment optimization.
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PMID:Cytotoxic activity of gemcitabine and correlation with expression profile of drug-related genes in human lymphoid cells. 1729 11


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