Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of glutathione was demonstrated histochemically in livers of rats treated with diethylnitrosamine or N-nitrosomorpholine. Glutathione content was markedly elevated in adenosine triphosphatase-deficient, gamma-glutamyltranspeptidase-positive hyperplastic cell islands. This finding may partly explain the increased resistance of hyperplastic cells to cytotoxic actions of hepatocarcinogens.
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PMID:Histochemical demonstration of enhanced glutathione content in enzyme-altered islands induced by carcinogens in rat liver. 610 9

This study was undertaken to answer the following question. Is the phenotypic diversity that is characteristic of hepatocellular carcinomas acquired early during carcinogenesis, or is it more likely to be a property added late in the process? This question was posed using a new model for the sequential analysis of hepatocarcinogenesis. This model utilizes a single initiating dose of a carcinogen, such as diethylnitrosamine, followed by the selective stimulation of the rare, initiated hepatocyte to proliferate under conditions in which the proliferation of the majority of uninitiated hepatocytes is inhibited. Under these conditions, discrete early foci of altered hepatocytes and hyperplastic foci and nodules are quite well synchronized for about 10 to 12 cell cycles, after which the synchrony is progressively lost. As phenotypic expressions, cell proliferation, judged by radioautography after the administration of [3H]thymidine and the activities of four enzyme markers, two positive ones, gamma-glutamyltranspeptidase and DT-diaphorase, and two negative ones, glucose-6-phosphatase and adenosine triphosphatase, all judged histochemically, were used. At the earliest time of observation, 7 days, and at subsequent time points thereafter, all histologically recognizable foci and nodules showed variable degrees of staining for each enzyme activity. Prior to selection, gamma-glutamyltranspeptidase activity was much more consistent than was that of the others; however, during and after the selection, the four markers showed almost the same consistency among developing lesions. During the period of selection, between 80 and 90% of hepatocytes in the proliferating nodules were labeled with [3H]thymidine, while only an occasional labeled hepatocyte was seen in the foci prior to selection and in the nodules following selection. In the postselection period, the majority of nodules acquired the histochemical and architectural properties of normal liver, while a minority persisted as typical hyperplastic nodules. This study suggests that phenotypes of carcinogen-altered hepatocytes are variable, but whether the histochemical diversity among the lesions is merely due to environmental variation or is a reflection of a more basic genotypic variability remains a fundamental question.
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PMID:Phenotypic diversity as an early property of putative preneoplastic hepatocyte populations in liver carcinogenesis. 611 Apr 77

The behavior of hyperplastic nodules following an in vivo short-term screening test for hepatocarcinogens was studied. Rats were injected ip with 200 mg/kg body weight of diethylnitrosamine (DEN), given basal diet containing 200 ppm of N-2-fluorenylacetamide (2-FAA) (group 1), 1000 ppm of the alpha-isomer of 1,2,3,4,5,6,-hexachlorocyclohexane (alpha-BHC) (group 2) or basal diet (group 3) from week 3 to week 8, and then given basal diet and tap water. They were subjected to partial hepatectomy at the end of week 3. Animals were killed at weeks 4, 6, 8, 10, 20, 30, 40, and 50. A significant disappearance of hyperplastic nodules following the cessation of carcinogen treatment was observed in group 1, but was not evident in groups 2 and 3. With gamma-glutamyltranspeptidase (GGTase) as a positive marker and adenosine triphosphatase (ATPase) as a negative marker, hyperplastic nodules were classified into 3 different phenotypic categories, i.e., (1) GGTase-positive and ATPase-negative, (2) GGTase-positive, and (3) ATPase-negative. The percentages of GGTase-positive and ATPase-negative hyperplastic nodules were almost 80 approximately 90% in group 1 and 70 approximately 80% in groups 2 and 3. Some of the hyperplastic nodules were necrotic from week 8 in groups 1 and 2, and from week 20 in group 3. Subsequently, the numbers of necrotic hyperplastic nodules increased with time. Hepatocellular carcinomas were found at weeks 30, 40, and 50 in group 1, and at weeks 40 and 50 in group 2. Significantly higher incidences of cancer were found in group 1 than in group 2. The hepatocellular carcinomas were also classified enzyme-histochemically into 3 different phenotypic categories as for hyperplastic nodules, but the percentage (20%) of GGTase-positive and ATPase-negative hepatocellular carcinomas was significantly lower than that (70 approximately 90%) of GGTase-positive and ATPase-negative hyperplastic nodules in each group.
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PMID:A sequential quantitative study of the reversibility or irreversibility of liver hyperplastic nodules in rats exposed to hepatocarcinogens. 611 91

In order to get precise information about the movement of plasma membrane proteins in cap formation, cyto- and bio-chemical analyses were made of the plasma membranes from non-capped areas of Ehrlich ascites tumor cells (EATCs) exposed to concanavalin A (Con A). Blebs formed by treatment with cytochalasin B (CB) of the non-capped areas of cells having a cap were isolated and used as the plasma membranes from non-capped areas (ConA-CB-bleb fraction). This bleb fraction was compared with a bleb fraction prepared from cells without ConA-treatment (CB-bleb fraction). Cytochemical analysis of ConA-CB-bleb fraction revealed a decreased in conA binding sites (ConA-BS) compared to the CB-bleb fraction. SDS polyacrylamide slab gel electrophoresis also revealed a decrease in the major components of ConA-BS of the ConA-CB-bleb fraction. The minor components of ConA-BS showed no distinct quantitative difference between the ConA-CB-bleb and CB-bleb fractions. NA+ K+-adenosine triphosphatase (ATPase), 5' nucleotidase (5'ND) and gamma-glutamyl transpeptidase (gamma-GTP) did not show any decrease in activity in the ConA-CB-bleb fraction, but the activity of D+-stimulated phosphatase (K-Pase) was decreased. The findings indicate that there are two types of plasma membrane glycoproteins in EATCs; one includes those participating in cap formation due to ConA, e.g. the major components of ConA-BS and K-Pase, and the other, those not participating in such cap formation, e.g. some minor components of ConA-BS, ATPase, 5'ND and gamma-GTP, which keep their places without moving.
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PMID:Movement of plasma membrane proteins of Ehrlich ascites tumor cells in relation to cap formation induced by concanavalin A: a study on the non-capped areas. 611 90

The activity of plasma membrane marker enzymes which are involved in purine metabolism (5'-nucleotidase, alkaline 5'-nucleotide phosphodiesterase), in active ion transport (Na-K-Mg-adenosine triphosphatase, ouabain-sensitive Na-K-adenosine triphosphatase), in aminoacid transport (gamma-glutamyltranspeptidase), and in basic physiologic functions (alkaline phosphomonoesterase) were assayed in mononuclear cells isolated from peripheral blood of normal donors and of patients with primary immunodeficiency. Irrespective of the clinical classification of the immunodeficiency, the cells of patients were characterized by significantly diminished 5'-nucleotidase and to a certain extent by lower alkaline phosphomonoesterase activities. Average activity levels of other enzymes were similar in cells of patients and controls, but scattering was more pronounced in the first group. Determination of substrate affinity revealed different kinetic properties of 5'-nucleotidase in cells from patients and normal donors; however, the extent of inhibition by beta-glycerophosphate or alpha, beta-adenosine-methylene diphosphate was comparable for both types of cells. The presence of inhibitory compounds in patients' serum was excluded by mixing experiments. When activities of the various plasma-membrane-associated enzymes were compared with each other, significant correlations emerged in normal lymphocytes. Most of these correlations were absent in cell membranes of immunodeficient patients. The findings indicate that the plasma membrane of lymphocytes from patients with immunodeficiency may be characterized by an altered distribution of enzymatic constituents.
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PMID:Correlations between enzymatic and immunologic properties of human peripheral blood mononuclear cells. I. Ectoenzymes of normal and immunodeficient peripheral blood mononuclear cells. 612 61

A plasma membrane fraction from the rat parotid gland has been prepared by a procedure which selectively enriches for large membrane sheets. This fraction appears to have preserved several ultrastructural features of the acinar cell surface observed in situ. Regions of membrane resembling the acinar luminal border appear as compartments containing microvillar invaginations, bounded by elements of the junctional complex, and from which basolateral membranes extend beyond the junctional complex either to contact other apical compartments or to terminate as free ends. Several additional morphological features of the apical compartments suggest that they are primarily derived from the surface of acinar cells, rather than from the minority of other salivary gland cell types. Enzymatic activities characteristically associated with other cellular organelles are found at only low levels in the plasma membrane fraction. The fraction is highly enriched in two enzyme activities--K+ -dependent p-nitrophenyl phosphatase (K+ -NPPase, shown to be Na+/K+ adenosine triphosphatase; 20-fold) and gamma-glutamyl transpeptidase (GGTPase; 26-fold)--both known to mark plasma membranes in other tissues. These activities exhibit different patterns of recovery during fractionation, suggesting their distinct distributions among parotid cellular membranes. Secretion granule membranes also exhibit GGTPase, but no detectable K+ -NPPase. Since Na+/K+ adenosine triphosphatase and GGTPase, respectively, mark the basolateral and apical cellular surfaces in other epithelia, we hypothesize that these two enzymes mark distinct domains in the parotid plasmalemma, and that GGTPase, as the putative apical marker, may signify a compositional overlap between the two types of membranes which fuse during exocytosis.
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PMID:Plasma membrane of the rat parotid gland: preparation and partial characterization of a fraction containing the secretory surface. 612 47

The influence of sodium phenobarbital (PB) treatment on the sequence of N-nitrosomorpholine (NNM) induced focal preneoplastic lesions in the rat liver was investigated using a combined morphological and enzyme histochemical approach. Quantitative assessment of the different types of foci of altered hepatocytes visible in H&E sections after carcinogen application, namely the clear and acidophilic cell glycogen storage foci and mixed cell foci comprising glycogen storing cells and also more basophilic hepatocytes showing reduction in glycogen reserves, revealed a shift towards mixed cell character and greater size in PB-treated livers in comparison to those receiving NNM alone. Within the three dose levels of PB investigated (0.75, 0.075 or 0.0075 g/l drinking water) a clear dose dependence in appearance of mixed cell foci was apparent. Assessment of alterations in the activities of marker enzymes observed within preneoplastic foci was carried out by comparison of PAS preparations with sections reacted for glucose-6-phosphate dehydrogenase (G6PDH), gamma-glutamyl transpeptidase, glucose-6-phosphatase and adenosine triphosphatase. G6PDH proved the most consistent enzyme marker for small glycogen storage foci whereas larger foci of that type and mixed cell foci were associated with change in activity of all enzymes studied. The results are discussed in relation to the sequence of events occurring during hepatocarcinogenesis and the influence of PB on altered cellular populations. The applicability of enzyme markers is further considered in view of the question of heterogeneity within populations of preneoplastic foci.
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PMID:Enhancement of NNM-induced carcinogenesis in the rat liver by phenobarbital: a combined morphological and enzyme histochemical approach. 613 86

Characteristic enzyme alterations have been demonstrated during the stages of experimental hepatocarcinogenesis in rats. The activity of gamma-glutamyl transpeptidase (GGTPase) in hyperplastic and neoplastic hepatocytes is usually increased, whereas that of canalicular adenosine triphosphatase (ATPase) and of glucose-6-phosphatase (G6Pase) is more variable. The activities of these marker enzymes were studied by histochemical techniques in 10 human hepatocellular carcinomas (HCCs), 1 liver cell adenoma, and 1 cholangiocarcinoma of liver. In 9 cases, the nontumorous liver was also examined. All HCCs, but not the liver cell adenoma, displayed enzyme patterns that differed from normal. GGTPase activity was markedly increased in 8 HCCs, whereas the activities of G6Pase and ATPase were lost in 6 and 8 HCCs, respectively. These enzyme alterations occurred as 5 of 7 possible combinations, resulting in significant heterogeneity of enzyme phenotypes, similar to that in experimental hepatocarcinogenesis.
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PMID:Enzyme patterns in human hepatocellular carcinoma. 624 71

The hypothesis that during the promotion phase of carcinogenesis a second rare event leads to a promoter-independent tumour cell was tested in an initiation-promotion-initiation type of experiment. Precancerous (island) cells induced in rat liver by 10 mg/kg N-nitrosodiethylamine given 24 h after partial hepatectomy were promoted by a protocol consisting of 2-acetylaminofluorene/partial hepatectomy. Administration of 25-100 mg/kg N-ethyl-N-nitrosourea served as second initiater. Microscopic foci of neoplastic cells were observed within the precancerous islands 66 days later; no such foci were noted in the appropriate controls. Deficiency of adenosine triphosphatase and glucose-6-phosphatase marker enzymes in the foci was more pronounced than in the surrounding island cells; glycogen storage was decreased and cytoplasmic basophilia slightly increased; gamma-glutamyltranspeptidase staining was negative or decreased with respect to the surrounding island cells, which exhibited a partially positive reaction. We conclude that a secondary change produced by N-ethyl-N-nitrosourea in precancerous island cells leads to focus-forming cells which grow, in the absence of promoter, into foci of neoplastic phenotype. Similar rare, initiation-like events might be involved in the process of tumour promotion in general.
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PMID:Initiation-promotion-initiation. Induction of neoplastic foci within islands of precancerous liver cells in the rat. 653 10

The effects of chronic alcohol consumption on nitrosamine metabolism in vivo, DNA synthesis and repair, and carcinogen-induced preneoplasia were studied in rat liver. Following a single injection of different doses of 14C-N-nitrosodimethylamine, there was no significant difference between controls and ethanol-pretreated rats in the alkylation pattern of cellular protein nor in the levels of the alkylation products 7-methylguanine and O6-methylguanine isolated from liver DNA. O6-Methylguanine-specific DNA repair was also unchanged. An increase in the number and size of foci staining negative for adenosine triphosphatase and/or positive for gamma-glutamyltranspeptidase was observed in rats treated intermittently with ethanol and N-nitrosomorpholine. The numbers of clear-cell and mixed-cell foci were also increased. An ethanol-mediated enhancement of DNA synthesis, which was ascertained by different methods, may be related to this cocarcinogenic action of the alcohol. Ethanol, however, failed to demonstrate promoting activity. Long-term treatment of carcinogen pretreated rats with ethanol, according to the classical initiation-promotion protocol, had no effect on the incidence of preneoplastic foci in liver.
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PMID:The mechanism of cocarcinogenic action of ethanol in rat liver. 653 12


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