Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:3.1.3.9 (
glucose-6-phosphatase
)
3,081
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A marked heterogeneity of enzyme histochemical phenotypes was demonstrated in 48 primary hepatocellular carcinomas induced by feeding 2-acetylaminofluorene to rats. All eight possible combinations of three abnormal traits, gain of
gamma-glutamyl transpeptidase
activity, loss of adenosine-5'-triphosphatase activity, and loss of
glucose-6-phosphatase
activity, were represented among the hepatocellular carcinomas. The four combinations in which two or three traits occurred together were seen in 85% of the carcinomas, while those categories with a normal phenotype or containing only single marker changes contained the few remaining neoplasms. As expected, the carcinomas all showed greatly increased and variable [3H]thymidine labeling indices; however, neither the rates of cell replication or the degrees of differentiation of the carcinomas appeared to correlate in any meaningful way with the patterns of phenotypic diversity. The distribution of histochemical phenotypes in the carcinomas differs greatly from that reported for enzyme-altered hyperplastic islands induced by carcinogens, but the significance of the difference is not apparent at the present time.
...
PMID:Enzyme histochemical phenotypes in primary hepatocellular carcinomas. 611 49
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.
...
PMID:Enhancement of NNM-induced carcinogenesis in the rat liver by phenobarbital: a combined morphological and enzyme histochemical approach. 613 86
Effect of chronic ethanol administration on some enzyme activities was studied in plasma membranes, brain homogenate cytoplasmic reticulum and cytosol, liver homogenate and microsomal fractions and blood serum. Ethanol was ingested as a constituent of isocaloric "semiliquid" diet. The investigation was carried out to estimate the diagnostic value of certain enzymes in evaluation of alcohol intoxication. In male rats ethanol caused remarkable hyperlipidemia, accumulation of lipids in liver tissue and elevation of
gamma-glutamyl transpeptidase
activity in blood serum and brain tissue. In liver tissue moderate induction of
glucose-6-phosphatase
, NADPH-cytochrome c reductase and alkaline phosphatase was observed. The putative mechanism of elevation of organospecific enzyme activities in blood serum during chronic ethanol consumption is discussed.
...
PMID:[Effect of chronic administration of ethanol on the enzyme activity of rat serum, liver and brain]. 614 65
The effects of a chronic 8- to 12-week administration of the hepatic tumor promoter, phenobarbital, on further altering the biochemical enzyme deviation patterns shown by hyperplastic liver nodules was examined in rats previously subjected to the initiation/selection protocol of Solt and Farber. Hyperplastic liver nodules of various size classes from the phenobarbital-treated group exhibited a significant increase in
GGT
specific activity, as well as 2- to 3-fold higher levels of microsomal cytochrome P-450 than was shown by control nodules. The increase in
GGT
specific activity was also found in many cases to be higher in those hyperplastic liver nodules from the phenobarbital-treated group with diameters greater than 3.0-3.5 mm than in nodules of a smaller size. In contrast, the
GGT
specific activity of the control nodules did not correlate with differences in their sizes. Furthermore, while histochemical staining of
GGT
activity appeared uniform in sections of the various sized hyperplastic nodules from the phenobarbital-treated group, biochemical measurements indicated a consistently higher specific activity for this enzyme in tissue taken from the central portion of the nodule than in tissue from the peripheral portion of the nodule. On the other hand, the specific activities of
glucose-6-phosphatase
, 5'-nucleotidase, and fructose-1,6-diphosphate aldolase of the hyperplastic liver nodules were not found to be significantly altered over control values by the chronic phenobarbital treatment, suggesting a stability of these other marker enzyme alterations during the early promotional phase of hepatocarcinogenesis.
...
PMID:Effect of phenobarbital on the altered biochemical phenotypes expressed by hyperplastic liver nodules during hepatocarcinogenesis in the rat. 614 62
The change in the activity of several hepatic enzymes during hepatocarcinogenesis suggests a pattern of dedifferentiation. This category of enzymes includes
glucose-6-phosphatase
and
gamma-glutamyltranspeptidase
(
GGT
). A detailed kinetic analysis of microsomal
glucose-6-phosphatase
activity revealed that both the translocase and phosphohydrolase activities were markedly reduced in Morris 7777 hepatoma transplanted in male Buffalo rats. In addition, the activity of the translocase component increased 2.4-fold, while the phosphohydrolase activity decreased 1.6-fold in the liver of tumor-bearing animals.
GGT
activity in the host liver was not effected by the presence of the tumor. These results suggest differences in the effect of Morris 7777 hepatoma on: the phosphohydrolase and translocase activities of microsomal
glucose-6-phosphatase
and the sensitivity of
glucose-6-phosphatase
and
GGT
activities in the host liver.
...
PMID:Effect of Morris 7777 hepatoma on microsomal glucose-6-phosphatase latent activity. 614 32
Fischer 344 male rats were treated with N-nitrosodiethylamine, and two weeks later promotion was effected by treatment with N-2-acetylaminofluorene for 14 days. At midpoint of the promotion protocol, one group of rats was subjected to partial hepatectomy (model A); others were treated with either carbon tetrachloride (model B) or thioacetamide (model C). Alterations in the activities of marker enzymes (
glucose-6-phosphatase
,
gamma-glutamyl transpeptidase
, cytochrome P-450, N-demethylase) during hepatocarcinogenesis were followed biochemically. The highest incidences of liver foci and of hepatocellular carcinomas were observed in model A, and these showed a good correlation with long-lasting elevated
gamma-glutamyl transpeptidase
activity. Analysis of the marker alterations suggests that there are three stages in hepatocarcinogenesis: (1) depression resulting from the toxic action of the initiator; (2) recovery and adaptation to cellular injury; and (3) long-lasting adverse alterations in the activities of the marker enzymes after promotion. The loss of certain non-histone proteins soon after promotion was also observed. Comparative studies of the individual actions of initiators and promoters on marker enzymes indicated that both contribute to the marker changes during hepatocarcinogenesis.
...
PMID:Alterations of markers during hepatocarcinogenesis in rats. 615 22
An oval cell-enriched population was isolated using two isopyknic centrifugation steps in Percoll gradients from the livers of young adult male rats maintained for 6 to 12 weeks on a choline-deficient diet containing 0.05% DL-ethionine. This cell population equilibrated sharply at densities ranging between 1.07 and 1.08 g/ml, possessed a mean cell diameter in fixed-cell smears of 13.6 micron, and showed viabilities of greater than 95% as judged by trypan blue dye exclusion. Contamination of this population by hepatocytes and Kupffer cells was determined to be less than 1% and between 4 and 14%, respectively. gamma-Glutamyl transpeptidase activity was demonstrated both biochemically and histochemically to be the most constant marker for evaluating the oval cell-enriched population isolated at various times over the 6 to 12 weeks of the choline-deficient/DL-ethionine dietary regimen. In contrast, the percentages of nonhepatocytic cells showing labeling for DNA synthesis and for alpha-fetoprotein were both found to be the highest in the oval cell-enriched population isolated at 6 weeks and lowest in that obtained at 12 weeks of dietary treatment. Furthermore, at 10 to 11 weeks, 19.2% of the nonhepatocytic cells in this population were positive for albumin, while 2.1% were positive for
glucose-6-phosphatase
activity, indicating some cells to be intermediate in function between the oval cell and the hepatocyte. In comparison, hyperplastic bile ductular epithelial cells in tissue preparations isolated from the livers of rats previously subjected to 13 weeks of chronic feeding of the noncarcinogenic cholestatic agent, 1-naphthyl isothiocyanate, or at 8 to 13 weeks following bile duct ligation were found to be strongly positive for
gamma-glutamyl transpeptidase
activity, as well as to be positive for alkaline phosphatase activity, but to be essentially negative for
glucose-6-phosphatase
activity, glycogen content, and albumin production. However, an occasional bile ductular cell in these preparations was found to exhibit a strong cytoplasmic binding of [6,7-3H]estradiol, an indirect measure of alpha-fetoprotein production. Also, a low, but demonstrable amount of DNA synthesis was noted in the bile ductular cells present in these preparations. Furthermore, a viable cell population highly enriched in bile ductular epithelial cells was isolated by isopyknic centrifugation in Percoll following enzymatic dissociation of the hyperplastic tissue preparation from bile duct ligated rats.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Isolation and partial characterizations of oval and hyperplastic bile ductular cell-enriched populations from the livers of carcinogen and noncarcinogen-treated rats. 620 45
Putative preneoplastic hepatocytes were isolated from male Fischer 344 rats treated with a single dose of diethylnitrosamine, 2-acetylaminofluorene feeding, and partial hepatectomy (Solt-Farber model). The isolation procedure involved, after collagenase dispersion of the liver, separation of the hepatocytes into small- and large-cell fractions by centrifugal elutriation, and subsequent selection of cells deficient in asialoglycoprotein receptor(s) by plating onto asialofetuin (ASF)-coated plates. The number of cell surface binding sites for the asialoglycoprotein receptor was measured with both asialoorosomucoid and ASF as ligands. There was a 50% reduction of binding sites for both ligands in the original cell suspensions obtained from preneoplastic livers. The reduction in receptor binding sites was most pronounced in the large cell fraction (less than or equal to 30% of control value) after separating the original cell suspension by elutriation into small and large cell fractions. Immunohistochemical studies showed a lack of asialoglycoprotein receptor in preneoplastic (i.e., hyperplastic foci) areas. These areas were entirely super-imposable with
glucose-6-phosphatase
-deficient areas and partially overlapped the
gamma-glutamyltranspeptidase
-positive areas in serial liver sections. The attachment of preneoplastic hepatocytes to ASF-coated tissue culture dishes was greatly impaired, and the number of
gamma-glutamyltranspeptidase
-positive cells on the ASF dishes was reduced to less than 7% as compared to 45 to 70% on the collagen-coated plates. Thus, the lack of asialoglycoprotein (asialofetuin) surface receptors and the increased size of the early preneoplastic hepatocytes are characteristics that can be used to separate the preneoplastic cell population from normal liver cells.
...
PMID:Isolation of preneoplastic rat liver cells by centrifugal elutriation and binding to asialofetuin. 620
Results of hepatocarcinogenesis studies are reviewed. The studies were made using different histochemical markers which permit revealing hyperplastic nodules in the liver. Determination of the
gamma-glutamyl transpeptidase
, ATPase,
glucose-6-phosphatase
activities and the glycogen, iron, alpha-fetoprotein contents are advisable when studying early changes in different cell populations during hepatocarcinogenesis.
...
PMID:[Early histochemical markers of hepatocarcinogenesis]. 620 85
Adult rat parenchymal hepatocytes in primary culture can be induced to enter into DNA synthesis and mitosis. The optimal conditions for hepatocyte replication are low plating density (less than 10,000 cells/sq cm) and 50% serum from two-thirds partially hepatectomized rats (48 hr after hepatectomy). Approximately 80% of the hepatocytes enter the cell cycle, and most of these cells go through mitosis. The replicating hepatocytes remain positive for
glucose-6-phosphatase
and negative for
gamma-glutamyl transpeptidase
, and they accumulate fat, in analogy to regenerating liver. Most of the replicating hepatocytes enter into multiple consecutive rounds of DNA synthesis. Dose-response studies between control animal serum and hepatocyte labeling index indicate that in unoperated animals the serum contains substances stimulatory as well as inhibitory for hepatic growth, with the inhibitory effect prevailing at high concentrations. After partial hepatectomy, the inhibitory activity disappears whereas the hepatopoietin activity reaches almost 90% of maximal biological effectiveness at 25% serum concentration. Addition of hormones to the system shows that the hepatopoietin activity is not identical to epidermal growth factor, platelet-derived growth factor, thyroxine, glucagon, or hydrocortisone. Norepinephrine abolishes the difference between control and hepatectomized serum but does not restore hepatopoietin activity when added to heat-inactivated serum. The results show that this system of replicating hepatocytes can be used to investigate the trophic factors that control growth of normal and neoplastic hepatocytes.
...
PMID:Liver regeneration studies with rat hepatocytes in primary culture. 621 20
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