Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of feeding hypolipidemic peroxisome proliferators on the induction of altered hepatic foci (AHF) in Fischer rats was studied in order to determine whether such agents can induce or promote the development of AHF. In the first study, rats were fed ciprofibrate (10 mg/kg/day) for 1 yr. AHF, neoplastic nodules, and hepatocellular carcinomas were induced. The presence of putative gamma-glutamyltranspeptidase (GGT) activity was numerically the most common marker, although it was absent in larger foci and nodules. A deficiency in canalicular ATPase and glucose-6-phosphatase provided the best markers for the larger foci and nodules. In the second study, rats were subjected to partial hepatectomy, and half of the animals were then intubated with diethylnitrosamine (10 mg/kg). One wk later, rats were fed Wy-14,643 at concentrations of 0, 0.05, and 0.1% in the diet for 6 mo. At 6 mo, the number and volume of foci were increased by the feeding of Wy-14,643 after partial hepatectomy alone and were greatly increased when Wy-14,643 was fed after partial hepatectomy/diethylnitrosamine administration. Canalicular adenosine triphosphatase and glucose-6-phosphatase deficiencies were the most common markers of AHF, and AHF of these phenotypes occupied practically all of the focal volume. The larger AHF did not express GGT, and those foci exhibiting GGT were much less common and occupied very little volume. The absence of the GGT protein itself, as opposed to an inhibition of GGT activity, was verified by immunohistochemical staining using an antibody to GGT. These studies show that hypolipidemic peroxisome proliferators can stimulate an increase in AHF following a single dose of diethylnitrosamine and a mitotic stimulus, and they thus can act as promoters in two-stage liver carcinogenesis. GGT is a poor marker for identifying AHF induced by peroxisome proliferators during the early, premalignant phase of hepatocarcinogenesis.
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PMID:Induction of altered hepatic foci in rats by the administration of hypolipidemic peroxisome proliferators alone or following a single dose of diethylnitrosamine. 287 87

Formation of the N-(deoxyguanosin-8-yl)-aminofluorene adduct was studied in enzyme-altered foci induced by four different liver carcinogenesis models. Foci were detected and scored for enzyme phenotype by a computer-aided image overlay technique. Localization of the enzymes gamma-glutamyl transpeptidase, canalicular ATPase and glucose-6-phosphatase was performed by enzyme histochemistry, allowing identification of foci of seven different phenotypes. Patterns of foci obtained by image overlay were compared to in situ 2-acetylaminofluorene--DNA adduct distribution obtained by immunofluorescence. Foci were induced by the following models: (1) chronic feeding of 0.02% 2-acetylaminofluorene (2-AAF) for 8 weeks; (2) intubation of diethylnitrosamine (DEN) (10 mg/kg) 24 h after a 70% partial hepatectomy (PH), followed 8 weeks later by a diet containing 0.05% phenobarbital for 9 months; (3) intubation of DEN (10 mg/kg) 24 h after PH, followed by a diet containing 0.01% ciprofibrate for 5 months, and after an additional 4 months a diet containing 0.05% phenobarbital for 2 months; (4) maintenance for 7.5, 16.5 or 19.5 months after transplantation of DEN/2-AAF/PH ('Solt-Farber' protocol) donor liver cells into host rats receiving a brief 2-AAF/PH selective regimen then no further treatment until sacrifice. To test the capacity of both foci and morphologically normal livers to form DNA adducts, the animals in models 2-4 received a diet containing 0.02% 2-AAF for 5 or 6 days before sacrifice. In all of the enzyme-altered foci identified in models 1-3 there were no DNA adducts visible by immunofluorescence. Scattered groups of positive cells were occasionally seen in the otherwise dark foci induced by model 4. For technical reasons some enzyme-altered foci were not identifiable on the fluorescence-stained slides. In liver serial sections from rats in models 1-4, there were 75, 304, 125 and 68 enzyme-altered foci of seven different phenotypes which were identified as AF-DNA negative. In models 1 and 4 there were some additional adduct-negative foci not associated with any of the seven identified focus phenotypes. These studies demonstrate that loss of the ability to form DNA adducts in hepatic enzyme-altered foci is a common and very early biochemical adaptation to xenobiotic exposure in different hepatocarcinogenesis models. This adaptation also is retained by the majority of foci in later stages of hepatocarcinogenesis.
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PMID:Lack of acetylaminofluorene--DNA adduct formation in enzyme-altered foci of rat liver. 289 93

Three enzyme makers, glucose-6-phosphatase, ATPase and gamma-glutamyl transpeptidase, have been used in studying carcinogenesis of hepatocellular carcinoma. They have been investigated in animal models and human hepatocellular carcinoma in vivo and in vitro. But the inconsistent levels of these three enzymes associated with this type of carcinoma raised the possibility that the carcinoma cells might have derived from the cells originating from different stages of differentiation. To evaluate this possibility, three human cell lines, Hep G2, Hep 3B, and HA 22T, all thought to be arrested in different stages of differentiation based on their biochemical and morphological characteristics, were used as models. The three enzyme markers glucose-6-phosphatase, ATPase and gamma-glutamyl transpeptidase were examined cytochemically and biochemically. Our results showed that there was no correlation between the ATPase levels and the stages of the cell line's differentiation. But both glucose-6-phosphatase and gamma-glutamyl-transpeptidase were higher in cells that were more differentiated.
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PMID:Cytochemical localization and biochemical analysis of the enzyme markers in human hepatoma cell lines. 290 58

The following enzymes have been studied (subcellular fractions are shown between parentheses): NAG and beta-glucuronidase (lysosomes); SDH (mitochondrial); glucose-6-phosphatase (endoplasmic reticulum); 5'-nucleotidase and (Na+, K+)Mg2+ ATPase (plasma membranes). Alterations on their activities were observed after subcutaneous injection of sex hormones, compared with controls. NAG activity from liver was always significantly decreased in lysosomal and microsomal fractions after the hormonal treatment. In the same conditions, NAG from brain was always increased. beta-Glucuronidase behaves like NAG in brain; in liver it was not modified by testosterone and it was slightly increased in lysosomal fraction after oestradiol treatment. SDH activity was not modified in mitochondrial fractions from liver, but this activity was always significantly increased in brain. Glucose-6-phosphatase activity was always significantly decreased in microsomal fractions from liver. It was increased in brain after oestradiol and testosterone injection, but medroxyprogesterone treatment caused a decreased activity. 5'-Nucleotidase and (Na+, K+)Mg2+ ATPase from brain were significantly increased in microsomal fractions by oestradiol and testosterone. Medroxyprogesterone, however, caused an increase in ATPase, but did not affect 5'-nucleotidase. Both activities in liver were decreased by oestradiol and increased by testosterone, but medroxyprogesterone caused (Na+, K+)Mg2+ ATPase to rise and 5'-nucleotidase to fall.
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PMID:Effects of oestradiol, testosterone and medroxyprogesterone on subcellular fraction marker enzyme activities from rat liver and brain. 298 29

The effect of subcutaneous injection of hydrocortisone and corticosterone on the activity values of some subcellular fractions marker enzymes from rat liver and brain was investigated and compared with controls (without treatment with hormones). The following enzymes were studied (subcellular fraction are shown between parentheses): N-acetyl-beta-D-glucosaminidase and beta-glucuronidase (lysosomes); succinate dehydrogenase = SDH (mitochondria); glucose-6-phosphatase (endoplasmic reticulum); 5'-nucleotidase and Na+-K+-Mg2+ ATPase (plasma membrane). The specific activity of lysosomal enzymes from liver showed no change when rats were injected either with hydrocortisone or corticosterone. The same enzymes from brain showed significant increases in their activities with both hydrocortisone or corticosterone except beta-glucuronidase; this enzyme gave activity values remaining between the control levels, after treatment with corticosterone. The activity of mitochondrial SDH was increased after corticosterone injection either in liver or brain. After hydrocortisone injection, its activity rises significantly in brain (72%), but it falls in liver compared to the control values. Glucose-6-phosphatase behaves similarly in brain or liver fractions; its activity increases always after corticosterone treatment and decreases by hydrocortisone. The plasma membrane marker enzymes did not change practically in brain fractions, excepted Na+-K+-Mg2+ ATPase which tends to rise its activity after hydrocortisone injection. In liver fractions, both 5'-nucleotidase and Na+-K+-Mg2+ ATPase activities increase either by corticosterone or hydrocortisone treatment, except 5'-nucleotidase which specific activity decreases in liver after hydrocortisone treatment.
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PMID:Alterations in the activities of subcellular fractions marker enzymes in rat liver and brain by hydrocortisone and corticosterone treatment. 298 17

Neoplastic liver cell colonies were induced in the livers of isogeneic F344 rats by intraportal injection of a hepatic cell suspension from diethylnitrosamine-treated donor rats. Examination of the livers 12 days after cell implantation revealed well-demarcated groups of liver cells. The colonies showed alterations of the normal hepatocyte phenotype, which were clearly demonstrated by histologic, cytochemical, and electron microscope techniques. The hepatocytes were markedly deficient in glucose-6-phosphatase and bile canalicular ATPase activities, and they contained numerous mitotic figures. Scanning and transmission electron microscopy allowed characterization of hepatocyte interfaces and the shape of sinusoids and the biliary network. The nodular colonies displayed disorganized, thickened trabeculae separated by dilated sinusoids. In these colonies the hepatocytes proliferated intensely and formed, inside the host parenchyma, revascularized, integrated nodular structures. However, these hepatocytes showed ultrastructural anomalies: large nuclei with prominent nucleoli, many free polysomes, and areas of proliferated smooth endoplasmic reticulum in connection with unfolded cisternae of the rough endoplasmic reticulum. All of these features agreed with the hypothesis previously proposed that the colonies may be precursors of the hepatocarcinomas that ultimately develop in animals given injections of treated liver cells. Direct confirmation, however, still is needed.
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PMID:Ultrastructural and cytochemical study of the early stages of liver colonization by transplanted neoplastic hepatocytes. 299 29

Alterations in the levels of selected enzymes have been studied in the liver, kidney and brain of mouse following mercuric chloride (1 mg/Kg body wt./d) administration for 10, 20 and 30 d. The activity of acid phosphatase increased in all the tissues, the highest increase was recorded in the kidneys which showed as much as 4.5 fold elevation following mercuric chloride administration for 30 d. Although the alkaline phosphatase activity in the liver and the brain increased following HgCl2 administration, the kidneys experienced a tremendous decline in this enzyme following the same treatment. Mercury-induced changes in ATPase were complex inasmuch as the nature and magnitude of these changes varied with the tissue as well as the duration of the treatment. Whereas the liver ATPase declined after all the treatment intervals, this enzyme increased in the kidney and brain following administration of HgCl2 for 10 d. However, both the kidneys and brain registered a substantial fall in ATPase activity when HgCl2 administration was continued for 30 d. The levels of both glucose-6-phosphatase and succinic dehydrogenase decreased in all the tissues following HgCl2 administration. Invariably, the magnitude of decrease was the highest after 30 d treatment with HgCl2.
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PMID:Enzyme changes in the brain, liver and kidney following repeated administration of mercuric chloride. 302 11

Zinc, lead and cadmium in the form of chloride salts when added to a standard assay system containing 80 X 10(-6) ejaculated washed human spermatozoa caused a dose and duration-dependent inhibition of their motility. The activity of certain key enzymes of carbohydrate and energy metabolism, viz, glycogen phosphorylase, glucose-6-phosphatase, fructose-1, 6-diphosphatase, glucose-6-phosphate isomerase, amylase, Mg2+- dependent ATPase and lactic and succinic acid dehydrogenases were also found to be inhibited. The order of inhibitory effects of the heavy metals were zinc less than lead less than cadmium. The metal chelating agent, ethylene diamine tetra-acetic acid (EDTA, disodium salt) also interfered with the spermatozoal motility and inhibited the enzyme activities.
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PMID:Effect of selected metal ions on the motility and carbohydrate metabolism of ejaculated human spermatozoa. 314 74

The relative potency of chemicals as promoting agents in multistage hepatocarcinogenesis has been previously defined as the Promotion Index through calculations of quantitative stereology. The Promotion Index is a function of the total cell population of altered hepatic foci in the liver at any given time and dose of promoting agent. When the Promotion Index was determined as a function of the dose of phenobarbital given in the diet for varying periods of time, a value of 394 was obtained for doses less than 0.01%; at doses between 0.01% and 0.1%, the Promotion Index was found to be 47. These values were obtained by the extrapolation of slopes of the Promotion Indices at various doses and durations of administration of phenobarbital. The volume percentages of the liver occupied by seven possible phenotypes using three different markers (gamma-glutamyltranspeptidase, canalicular ATPase and glucose-6-phosphatase) were relatively constant in distribution for up to one year of phenobarbital administration except at the two highest doses employed, 0.5% and 0.1%, at which a maximal effect of the promoting agent has been obtained. Possible mechanisms for the biphasic relationship of the Promotion Index of phenobarbital with the dose and time of administration are discussed.
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PMID:The effects of dose and duration of administration on the promotion index of phenobarbital in multistage hepatocarcinogenesis in the rat. 317 34

The clonality of chemically induced altered hepatocellular foci was examined in rat liver. Chimeric rats composed of two histologically distinguishable cell lineages were placed on an initiation-promotion protocol for liver cancer induction. This resulted in multiple lesions of altered enzyme expression. These altered hepatocellular foci are generally considered to be initiated sites susceptible to cancer formation. The cellular origins of these lesions were determined by aligning sections demonstrating cell lineage with serial sections stained for altered enzyme expression. Analysis included 110 areas of deficient ATPase (EC 3.6.1.3) activity and 59 glucose-6-phosphatase (EC 3.1.3.9; G-6-Pase) deficient lesions, 744 foci of re-expression of gamma-glutamyl transpeptidase (EC 2.3.2.2; gamma-GT), and decreased glycogen mobilization (187 lesions). Of the 1100 focal enzyme alterations, 1054 were shown to be composed entirely of cells from a single lineage of the two lineages present in the mosaic tissue. Multiple alterations occurred within given lesions. Lesions with up to four phenotypic alterations were found to consist of cells of a single lineage. These results suggest that individual enzyme-altered foci are clonal in origin and that phenotypic heterogeneity within altered hepatocellular foci is due to lesion progression within a clonal population and not to a multicellular derivation.
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PMID:Clonality of preneoplastic liver lesions: histological analysis in chimeric rats. 319 1


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