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)

Ischemic preconditioning has been proposed to protect the heart against infarction by increasing 5'-nucleotidase (5'-NT) activities and augmenting adenosine levels during sustained coronary artery occlusion. To test this theory, anesthetized dogs received four 5-min episodes of preconditioning ischemia, pretreatment with the pharmacological "preconditioning mimetic" monophosphoryl lipid A (MLA, 35 micrograms/kg i.v.) or no intervention before coronary artery ligation. At 20 min into occlusion (the crucial time at which myocyte death begins in this model), myocardial samples were obtained for measurement (by high-performance liquid chromatography) of ectosolic and cytosolic 5'-NT activity and adenosine levels. Preconditioning and MLA pretreatment limit infarct size in the canine model by 75 and 50%, respectively. However, only MLA augmented 5'-NT activity [i.e., cytosolic 5'-NT in the ischemic subendocardium was 26 +/- 1, 39 +/- 7, and 26 +/- 6 nmol. mg protein-1. min-1 in preconditioned, MLA, and control groups (P < 0.05), respectively]. Moreover, adenosine levels (in nmol/mg protein) were increased with MLA treatment (2.30 +/- 0.44) but attenuated in preconditioned dogs (1.11 +/- 0.23; P < 0.05) versus controls (1.87 +/- 0.29). Thus 5'-NT and adenosine levels need not be increased beyond control values during sustained occlusion to elicit cardioprotection.
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PMID:Disparate effects of preconditioning and MLA on 5'-NT and adenosine levels during coronary occlusion. 927 14

A unifying hypothesis is presented postulating an apocrine release of several seminal proteins which mix and reaggregate in seminal fluid, thereby eventually forming particles designated either as "prostasomes", "vesiculosomes" or "seminosomes". The term "aposomes" should be restricted to the blebs released from secretory cells in the rat dorsal prostate and coagulating gland. Three different proteins present in human seminosomes along with the respective antibodies have been used to identify the localization, function and hypothetical interaction with spermatozoa. The proteins were (1) seminal vesicle-derived fibronectin, (2) prostate-derived 5'-nucleotidase and (3) a hitherto unidentified 100 kD membrane protein from epididymis, seminal vesicle and prostate. I. Fibronectin is an extracellular matrix protein which is also secreted from the seminal vesicles participating in the formation of the seminal clot. Immunofluorescence and immunoelectron microscopy revealed a relatively broad distribution pattern of fibronectin immunoreactivity on spermatozoa from different donors. Adding a fibronectin antiserum at a moderate dilution to vital spermatozoa in vitro resulted in a significant increase in sperm motility. Purified plasma fibronectin added at various concentrations to a vital sperm preparation was found to inhibit sperm motility in a dose-dependent manner. Measurement of calcium fluxes in individual sperm in the presence of fibronectin showed a significant increase. These findings point to a possible post-testicular regulatory function of seminal fibronectin. 2.5'-Nucleotidase (5'-NT) is an enzyme that hydrolyzes nucleotides such as AMP or IMP into inorganic phosphate and the respective nucleoside. The highest amount and activity of 5'-nucleotidase was present in glandular cells of the prostate; much less was detected in seminal vesicles and epididymis. On spermatozoa, the enzyme was localized on the outer leaflet of the plasma membrane covering the acrosomal region. Addition of purified enzyme to an in vitro incubation system of spermatozoa had no effect on sperm motility. A slight reduction of overall motility, however, was observed after addition of 5'-NT antibody to the spermatozoa. When 5'-nucleotidase inhibitors and adenosine channel antagonists were added to the sperm incubation system, a clear-cut inhibition of sperm motility occurred in a dose-dependent manner. This result is interpreted as indicating a significant role of ecto-5'-nucleotidase in the regulation of sperm motility. 3. A polyvalent antiserum against native human prostasomes recognized antigens in the range of 10-14 kD and of approximately 100 kD, respectively, in seminal fluid and prostate homogenates. Immunohistochemical studies revealed the presence of respective antigens in the epididymis, seminal vesicles and the prostate. Immunoelectron microscopy of ultracryo-sections showed labeling both of the apical plasma membrane in the prostate, as well as intraluminal secretory particles indicating the apocrine i.e. plasma-membrane bounded release of these particles. The secretory elements are termed "seminosomes". An affinity-purified fraction within the antiserum recognizes a 100 kD protein which is present both in the apical plasma membrane of the male genital glands, but also in the sperm head and principal piece of human spermatozoa. Incubation of spermatozoa with seminosomes and the respective purified antiserum had no effect on sperm motility. This is in contradistinction to former reports on motility increase induced by the so-called prostasomes.
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PMID:The role of apocrine released proteins in the post-testicular regulation of human sperm function. 936 95

The hydrolysis of AMP to adenosine during acute coronary underperfusion is temporarily beneficial to myocardial survival yet may cause tissue injury during sustained underperfusion because of depletion of adenine nucleotides. We hypothesized that the enzyme mediating AMP hydrolysis, 5'-nucleotidase (5'-NT), is downregulated during sustained coronary underperfusion to prevent excessive loss of nucleotides. Langendorff-perfused rabbit hearts were subjected to two successive, identical 45-min periods of underperfusion (4-5% of baseline flow) separated by 20 min of reperfusion. Although coronary venous lactate efflux was comparable in the two periods, total coronary purine efflux during the second period of underperfusion was attenuated by 75%. Phosphorus nuclear magnetic resonance data showed that ATP fell 46% in the first period but fell only another 10% in the second period. Phosphocreatine levels fell comparably (75-78%) during both periods of underperfusion. Analysis using a mathematical model describing the kinetics of myocardial energetics revealed that the combined data set was best described by a lower activity of 5'-NT (52% decrease in maximal reaction velocity) during the second period of under-perfusion. Additional time course experiments showed that the decrease in 5'-NT activity was slow in onset, requiring approximately 20 min of underperfusion. The decrease in 5'-NT activity during sustained underperfusion may benefit tissue survival by limiting the depletion of myocardial adenine nucleotides. In conclusion, at the onset of coronary underperfusion, there is a high activity of 5'-NT, but later during sustained under-perfusion, 5'-NT is downregulated, resulting in decreased AMP hydrolysis to adenosine.
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PMID:Downregulation of 5'-nucleotidase in rabbit heart during coronary underperfusion. 948 57

The ability to resynthesize ATP during recovery from ischemia is limited to the size of endogenous pool of adenine nucleotides. Cytosolic AMP-specific 5'-nucleotidase (5'-NT) plays a key role in ATP degradation and hence the capacity for ATP resynthesis. We have suggested (J. Clin. Invest. 93: 40-49, 1994) that intracellular acidosis [intracellular pH (pHi)] is a potent inhibitor of 5'-NT under in vivo conditions. To test this hypothesis further, we used the hyperthyroid rat heart because we could alter pHi during ischemia and determine the consequences of lower pHi on AMP accumulation (by chemical assay) and ATP resynthesis (by 31P nuclear magnetic resonance spectroscopy) during reperfusion. Global no-flow ischemia caused pHi to decrease from 7.1 under well-oxygenated control perfusion to 6.7. We found that decreasing pHi further from pH 6.7 to 6.4 leads to increased accumulation (30%) of AMP during ischemia and to a 2.5-fold increase in ATP resynthesis during reperfusion. Analysis of all known substrates, products, activators, and inhibitors of the 5'-NT suggests that 5'-NT is activated primarily by Mg2+ and ADP and is inhibited by H+. Thus these observations provide evidence for a salutary effect of intracellular acidosis on preserving the AMP pool due to inhibition of 5'-NT and suggest a novel role of H+ in protecting ischemic tissue.
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PMID:Regulation of cardiac AMP-specific 5'-nucleotidase during ischemia mediates ATP resynthesis on reflow. 957 96

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

High energy phosphate levels fall rapidly during cardiac ischemia and recover slowly (more than one week) during reperfusion. The slow recovery of ATP may reflect a lack of purine metabolic precursors and/or increased activity of purine catabolic enzymes such as 5'-nucleotidase (5'-NT, EC 3.1.3.5) and adenosine deaminase (ADA, EC 3.5.4.4). The activity of enzymes involved in both the catabolism of ATP precursors (5-NT and ADA) and the restoration of ATP from slow synthetic pathways [adenosine kinase (AK, EC 2.7.1.20), adenine phosphoribosyl transferase (APRT, EC 2.4.2.7) and hypoxanthine phosphoribosyl transferase (HPRT, EC 2.4.2.8)] may directly affect the rate of ATP recovery. Strategies to enhance recovery will depend on the relative activity of these enzymes following ischemia. Their activity in different species and their response to ischemia are not well characterized. Hence, rapid assay methods for these enzymes would facilitate detailed time course studies of their activities in postischemic myocardium. We modified a single ion-exchange column chromatographic method using DEAE-Sephadex to determine the products of incubation of 5'-NT, AK, APRT and HPRT with their respective substrates. The uniformity of the final product measurement procedure for all assays permits the activities of the four enzymes to be rapidly determined in a single tissue sample and facilitates the study of a large number of samples. This technique should also be useful for enzymes of the pyrimidine metabolic pathway.
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PMID:Ion-exchange column chromatographic method for assaying purine metabolic pathway enzymes. 961 62

Human 5'-nucleotidase (5'-NT, EC 3.1.3.5) is an enzyme that hydrolyzes nucleotides such as AMP or IMP (inosine 5'-monophosphate) into inorganic phosphate and the respective nucleoside. It has been suggested that the enzyme acts as a scavenger of injured cell or membrane components or as a supplier of adenosine. We have purified to homogeneity human 5'-NT, a 69-kDa glycoprotein containing a glycosylphosphatidylinositol anchor, present in human seminal fluid. With use of a polyclonal rabbit antiserum against the protein, a strong immunoreaction was detected in prostatic epithelium, exceeding that in placental syncytiotrophoblast and amnion cells. A slightly less intense immunoreaction was present in some cells of seminal vesicle epithelium and in vesicular intraluminal secretion. In the epididymis, only the apical cell portion and particularly the stereocilia of the epididymal principal cells, as well as clusters of small nonciliated cells in the efferent ductules, were immunoreactive. In the testis, no immunoreactive cells at all were detected, and likewise no clear-cut signal was observed in testicular and epididymal spermatozoa. The immunohistochemical results were coincident with Western blots prepared from homogenates of the respective tissues. Reverse transcription-polymerase chain reaction studies were performed with primers derived from the sequence of human placental ecto 5'-NT. Using human placenta as a reference tissue, positive results were obtained in the epididymis, seminal vesicle, and prostate, but not in the testis. On Northern blots, we determined the size of the mRNA at 2.4 kilobases. The relatively strong expression of 5'-NT in the human male accessory sex glands points to a potential regulatory role of the enzyme during posttesticular modification of the sperm surface.
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PMID:Expression and enzymic activity of ecto 5'-nucleotidase in the human male genital tract. 967 11

Cellular redox status and membrane protein activities were analyzed in kidneys from rats with ischemic acute renal failure (ARF). ARF was induced by clamping the left renal artery for 50 min. A parallel group of control animals was processed. In the ischemic group urea plasma levels were statistically increased as compared with the control group. Studies employing whole kidney homogenates revealed that ischemia produces an increment in lipid peroxidation levels and a reduction in glutathione concentration and in superoxide dismutase and glutathione peroxidase activities. Since lipid peroxidation may alter the function of membrane proteins we determined succinate cytochrome c reductase (SuccR), sodium-potassium ATPase (Na-K-ATPase), glucose-6-phosphatase (G-6-Pase) and alkaline phosphatase (ALP) activities in whole renal homogenates. Only G-6-Pase and ALP activities were modified by ischemia. Since ALP is a brush border membrane (BBM) enzyme and BBM is one of the main target structures in ARF, we assessed some parameters of BBM functionality. ALP, gamma-glutamyl transferase (gamma-GT) and 5'-nucleotidase (5'-NT) showed diminished activities in BBM from ischemic kidneys. Ischemia also modified the Vmax of paraaminohippuric acid (PAH) uptake without altering Km. An increment of lipid peroxidation and membrane fluidity in BBM was observed after the treatment. Total membrane proteins and protein recoveries in BBM were similar in both experimental groups. Sialic acid and sulfhydryl levels were similar in BBM from ischemic kidney and control ones. In summary, ARF induced by renal artery clamping for 50 min takes place with a significant increase in urea plasma levels. A decrease in the antioxidant defense system is detected. This induces lipid peroxidation in whole renal tissue, which may justify the diminished activities of some membrane enzymes such as G-6-Pase and ALP. A specific analysis of BBM function reveals a significant increment of lipid peroxidation which may be the cause of an increased membrane fluidity. This latter parameter might be, at least in part, responsible for the damaged function of apical ALP, 5'-NT, gamma-GT and PAH carrier.
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PMID:Impairment of cellular redox status and membrane protein activities in kidneys from rats with ischemic acute renal failure. 968 97

This report describes the subcellular distribution of 5'-nucleotidase (5'-NT) in rat photoreceptor cells and pigment epithelial cells processed by rapid-freeze enzyme cytochemistry. There was a striking difference in the ultrastructural localization of 5'-NT activity between rod outer segments after freeze-substitution fixation and conventional fixation. By rapid-freezing enzyme cytochemistry, 5'-NT activity was localized in the extradiscal space of intact nonvacuolated discs, whereas by conventional cytochemistry it was shown in the intradiscal space of artifactual vacuolated discs. In the freeze-substituted retinal cells, an appreciable difference in functional 5'-NT molecules was also found. The soluble 5'-NT on the cytoplasmic side of the disc membrane was vital in the rod outer segments, whereas the membrane-bound ecto-5'-NT on the exoplasmic (external) surface of the apical process was active in the pigment epithelial cells. Rapid-freezing enzyme cytochemistry should be worth employing as a method to reveal the fine localization of enzyme activity at the level of cell ultrastructures, which are poorly preserved by conventional fixation, and should provide information approximate to that in living cells.
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PMID:5'-nucleotidase in rat photoreceptor cells and pigment epithelial cells processed by rapid-freezing enzyme cytochemistry. 970 76

The activities of 2-chlorodeoxyadenosine (2-CdA) metabolizing enzymes, deoxycytidine kinase (dCK) and cytosolic 5'-nucleotidase (5'-NT) were measured in control and bryostatin 1 treated CLL cells using an EBV-negative WSU-CLL cell line. This cell line was established from a patient with CLL resistant to fludarabine. The results revealed a significant increase in dCK activity in bryostatin 1 treated cells at 48 and 72 h compared with the control. 5'-NT activity decreased significantly at 48 h. The ratio of dCK to 5'-NT activity was significantly increased in bryostatin 1 treated WSU-CLL cells after 48 h. WSU-CLL cells treated with bryostatin 1 exhibited an increase in the percentage of apoptotic and dead cells from control levels of 16% to 40%. This percentage was further increased to 67% following the addition of 11.2 microM 2-CdA to WSU-CLL cells pretreated with bryostatin 1. Results from Western blot analysis indicate that WSU-CLL cells express high levels of Bcl-2, Bcl-xL and c-myc, and a low level of Bax. p53 in untreated WSU-CLL cells is undetectable. WSU-CLL cells treated with bryostatin 1 showed a significant increase in the ratio of Bax to Bcl-2. To demonstrate that the bryostatin 1 mediated enhancement of 2-CdA efficacy was not restricted to in vitro cell culture, we have studied the tumor growth delay of WSU-CLL xenografts treated with placebo, bryostatin 1, 2-CdA, and bryostatin 1 followed by 2-CdA. SCID mice given bryostatin 1 at 75 microg x kg(-1) x d(-1) for 5 days followed by 30 mg x kg(-1) x d(-1) 2-CdA for 5 days in two cycles, had significantly improved tumor growth delay (P = 0.05). We conclude that bryostatin 1 is not only capable of inducing apoptosis by itself, but also sensitizes de novo resistant WSU-CLL cells to the chemo-therapeutic effects of 2-CdA. The bryostatin 1-induced increased ratio of dCK/5'-NT activity and an increased ratio of Bax/Bcl-2 are at least two mechanisms through which this natural compound is able to potentiate the anti-tumor activity of 2-CdA in otherwise resistant CLL cells.
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PMID:Potentiation of 2-chlorodeoxyadenosine activity by bryostatin 1 in the resistant chronic lymphocytic leukemia cell line (WSU-CLL): association with increased ratios of dCK/5'-NT and Bax/Bcl-2. 982 May 86


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