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)

Comparison of membrane bound 5'-nucleotidase activity has been made in crude extracts and plasma membrane fractions from Abelson virus transformed lymphomas, IgM, IgG and IgA producing plasmacytomas and from thymomas with different surface antigen markers. 5'Nucleotidase activity was characterised by the following criteria : 1) optimal pH for enzyme activity, 2) specificity of 5'AMP as a substrate at the optimal pH, 3) specific inhibition of the enzyme by alpha beta methylene ADP, 4) inhibition by EDTA. 5'-Nucleotidase was found to be present on the following B cells : Abelson virus transformed lymphomas, plasmacytomas and LPS-stimulated blasts from nu/nu spleens. The enzyme was also found in one thymoma Lut 13, but it was absent from all the other thymomas studied. A possible relationship between 5'-Nucleotidase and purine metabolism in lymphocyte subpopulations is suggested by the results.
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PMID:Plasma membrane enzymes in BALB/c lymphomas with either T or B cell properties, I. 5'-Nucleotidase. 627 Mar 28

Mouse peritoneal macrophages elicited by injecting i.p. killed group C Streptococci were shown to exhibit several characteristics commonly found in inflammatory macrophages: they secreted high levels of plasminogen activator but had to be stimulated in vitro by LPS to elaborate significant amounts of lymphocyte activating factor (LAF); they contained increased acid hydrolase activities as compared to resident macrophages whereas ecto 5'-nucleotidase was diminished; and they released less arachidonic acid oxygenation products than resident macrophages. However, they also expressed biochemical and functional properties attributed to classically activated macrophages, harvested from immune animals: they displayed reduced levels of alkaline phosphodiesterase; when suitably triggered, they released large quantities of H2O2; and they were strongly cytostatic to syngeneic tumor cells.
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PMID:Stimulation of several functional properties of macrophages after injection of a suspension of killed Streptococci. 676 35

Insufficient glutamine for the lungs during sepsis may contribute to an impairment in lung function. Lung glutamine metabolism is supported by both blood glutamine uptake and de novo biosynthesis using circulating glutamate as a precursor. Information regarding the specific plasma membrane carriers involved in this uptake is lacking. Furthermore, the effect of sepsis on amino acid transport in whole lung has not been studied. We isolated lung plasma membrane vesicles (LPMVs) from control and LPS-treated rats and assayed glutamine and glutamate transport activity in LPMVs. Vesicle purity and functionality were confirmed by time-dependent concentrative amino acid uptake in the presence of Na+, impoverishment of microsomal enzymes, and a 25-fold enrichment in the plasma membrane marker 5'-nucleotidase. Eighty percent of glutamine uptake in lung vesicles was mediated via the high affinity Na(+)-dependent carrier System ASC (Vmax = 80 +/- 10 pmole/mg protein/15 sec; Km = 224 +/- 30 microM) while 19% occurred via the Na(+)-independent System ASC (Vmax = 11 +/- 2 pmole/mg/15 sec; Km = 141 +/- 23 microM). Ninety percent of glutamate transport was mediated by the Na(+)-independent System XAG-. Treatment of rats with LPS resulted in a decrease in both glutamine and glutamate transport in LPMVs. LPMVs offer a novel method for characterizing lung amino acid transport and studying the effects of catabolic states on this activity. The effects of endotoxin on System ASC and XAG- activity may contribute to reduced lung glutamine availability during septic states which may impair cellular metabolism and function.
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PMID:Characterization of glutamine and glutamate transport in rat lung plasma membrane vesicles. 922 17

Bacterial endotoxin (lipopolysaccharide; LPS) given to animals in large doses results in pronounced, midzonal liver injury. Exposure to smaller, non-injurious doses of LPS augments the toxicity of certain hepatotoxicants. This study was conducted to delineate the development of injury in a rat model of augmentation of aflatoxin B(1) (AFB(1)) hepatotoxicity by LPS. At large doses (i.e., > 1 mg/kg, ip), AFB(1) administration resulted in pronounced injury to the periportal regions of the liver. Male, Sprague-Dawley rats (250-350 g) were treated with 1 mg AFB(1)/kg, ip or its vehicle (0.5% DMSO/saline) and 4 h later with either E. coli LPS (7.4 x 106 EU/kg, iv) or its saline vehicle. Liver injury was assessed 6, 12, 24, 48, 72, or 96 h after AFB(1) administration. Hepatic parenchymal cell injury was evaluated as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum and from histologic examination of liver sections. Biliary tract alterations were evaluated as increased concentration of serum bile acids and activities of gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and 5'-nucleotidase (5'-ND) in serum. At all times and for all markers, injury in rats treated with either AFB(1) or LPS alone was absent or modest. In the AFB(1)/LPS cotreated group, hepatic parenchymal cell injury was pronounced by 24 h and had returned to control values by 72 h. The injury began in the periportal region and spread midzonally with time. Furthermore, changes in serum markers indicative of biliary tract alterations were evident by 12 h and had returned to control values by 72 h. Thus, the nature of the hepatic lesions suggested that LPS potentiated the effects of AFB(1) on both parenchymal and bile duct epithelial cells.
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PMID:Bacterial lipopolysaccharide exposure augments aflatoxin B(1)-induced liver injury. 1082 77

Exposure to small, noninjurious doses of the inflammagen, bacterial endotoxin (lipopolysaccharide, LPS) augments the toxicity of certain hepatotoxicants including aflatoxin B(1) (AFB(1)). Mediators of inflammation, in particular neutrophils (PMNs), are responsible for tissue injury in a variety of animal models. This study was conducted to examine the role of PMNs in the pathogenesis of hepatic injury after AFB(1)/LPS cotreatment. Male, Sprague-Dawley rats (250-350 g) were treated with either 1 mg AFB(1)/kg, ip or its vehicle (0.5% DMSO/saline), and 4 h later with either E. coli LPS (7. 4 x 10(6) EU/kg, iv) or its saline vehicle. Over a course of 6 to 96 h after AFB(1) administration, rats were killed and livers were stained immunohistochemically for PMNs. LPS resulted in an increase in PMN accumulation in the liver that preceded the onset of liver injury. To assess if PMNs contributed to the pathogenesis, an anti-PMN antibody was administered to reduce PMN numbers in blood and liver, and injury was evaluated. Hepatic parenchymal cell injury was evaluated as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum and from histologic examination of liver sections. Biliary tract alterations were evaluated as increased concentration of serum bile acids and activities of gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and 5'-nucleotidase (5'-ND) in serum. Neutrophil depletion protected against hepatic parenchymal cell injury caused by AFB(1)/LPS cotreatment but not against markers of biliary tract injury. This suggests that LPS augments AFB(1) hepatotoxicity through two mechanisms: one of which is PMN-dependent, and another that is not.
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PMID:Lipopolysaccharide augments aflatoxin B(1)-induced liver injury through neutrophil-dependent and -independent mechanisms. 1105 57

CD73 (ecto-5'-nucleotidase; EC 3.1.3.5) participates in lymphocyte binding to endothelial cells and converts extracellular AMP into a potent anti-inflammatory substance adenosine. However, the regulation of expression and function of CD73 has remained largely unknown. In this study, we show that IFN-alpha produces a time- and dose-dependent long-term up-regulation of CD73 on endothelial cells, but not on lymphocytes both at protein and RNA levels. Moreover, CD73-mediated production of adenosine is increased after IFN-alpha treatment on endothelial cells, resulting in a decrease in the permeability of these cells. Subsequent to induction with PMA, FMLP, dibutyryl cAMP, thrombin, histamine, IL-1beta, TNF-alpha, and LPS, no marked changes in the level of CD73 expression on endothelial cells are observed. We also show that CD73 is up-regulated in vivo on the vasculature after intravesical treatment of urinary bladder cancers with IFN-alpha. In conclusion, distinct behavior of lymphocyte and endothelial CD73 subsequent to cytokine treatment further emphasizes the existence of cell type-specific mechanisms in the regulation of CD73 expression and function. Overall, these results suggest that IFN-alpha is a relevant in vivo regulator of CD73 in the endothelial-leukocyte microenvironment in infections/inflammations, and thus has a fundamental role in controlling the extent of inflammation via CD73-dependent adenosine production.
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PMID:IFN-alpha induced adenosine production on the endothelium: a mechanism mediated by CD73 (ecto-5'-nucleotidase) up-regulation. 1473 46

Macrophages are key elements in the inflammatory process, whereas depending on the micro-environmental stimulation they exhibit a pro-inflammatory (classical/M1) or an anti-inflammatory/reparatory (alternative/M2) phenotype. Extracellular ATP can act as a danger signal whereas adenosine generally serves as a negative feedback mechanism to limit inflammation. The local increase in nucleotides communication is controlled by ectonucleotidases, such as members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family and ecto-5'-nucleotidase/CD73 (ecto-5'-NT). In the present work we evaluated the presence of these enzymes in resident mice M1 (macrophages stimulated with LPS), and M2 (macrophages stimulated with IL-4) macrophages. Macrophages were collected by a lavage of the mice (6-8 weeks) peritoneal cavity and treated for 24 h with IL-4 (10 ng/mL) or LPS (10 ng/mL). Nitrite concentrations were measured using the Greiss reaction. Supernatants were harvested to determine cytokines and the ATPase, ADPase and AMPase activities were determined by the malachite green method and HPLC analysis. The expression of selected surface proteins was evaluated by flow cytometry. The results reveal that M1 macrophages presented a decreased ATP and AMP hydrolysis in agreement with a decrease in NTPDase1, -3 and ecto-5'-nucleotidase expression compared to M2. In contrast, M2 macrophages showed a higher ATP and AMP hydrolysis and increased NTPDase1, -3 and ecto-5'-nucleotidase expression compared to M1 macrophages. Therefore, macrophages of the M1 phenotype lead to an accumulation of ATP while macrophages of the M2 phenotype may rapidly convert ATP to adenosine. The results also showed that P1 and P2 purinoreceptors present the same mRNA profile in both phenotypes. In addition, M2 macrophages, which have a higher ATPase activity, were less sensitive to cell death. In conclusion, these changes in ectoenzyme activities might allow macrophages to adjust the outcome of the extracellular purinergic cascade in order to fine-tune their functions during the inflammatory set.
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PMID:Differential macrophage activation alters the expression profile of NTPDase and ecto-5'-nucleotidase. 2234 56