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:3.1.3.9 (glucose-6-phosphatase)
3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse renal cell tumors (RCT) were induced in male CBA male mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH) per kg body weight once a week. After a lag period of two years the kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: Glycogen content, basophilia, and activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline phosphatase (ALPase) and glutamyl-transpeptidase (GGT). RCT displayed the same histochemical profile irrespective of their size and growth pattern. In comparison with normal kidney epithelium, the neoplastic cells exhibited elevated activities of enzymes for glycolysis (HK, PK LDH) and the pentose phosphate pathway (G6PDH) while negative G6Pase and low SDH activity were observed in these cells. The majority of RCT showed high PHO activity and weak staining for SYN. Activities of ALPase and GGT were negative in most of the RCT. Giant cells were detected in some large RCT. Higher activities of glycolytic and mitochondrial enzymes and G6PDH were found in giant cells compared with other tumor cells. Tubular preneoplastic lesions were similar to neoplastic lesions in morphological and histochemical characteristics. The present study revealed that a markedly elevated capacity for glycolysis and the pentose phosphate pathway occurred in renal cell tumors in mice. A similar histochemical pattern in the few preneoplastic tubular lesions observed suggests that these metabolic aberrations emerge early in carcinogenesis, but studies on earlier stages of renal carcinogenesis are needed to substantiate this assumption.
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PMID:[Enzymic spectrum of preneoplastic and neoplastic changes induced by 1,2-dimethylhydrazine in mouse kidneys]. 874 89

The development of new diagnostic/therapeutic modalities for cancer requires a specific understanding of how tumors differ from normal tissues. Though the key components involved in the selective accumulation of 2-deoxy-D-glucose (2-DG) analogs in tumors are known, the relative importance of each is controversial. For this reason glucose transport protein (GLUT) density, hexokinase/glucose-6-phosphatase (GP) activity, and 2-DG biodistribution were measured together in four tumor models and normal murine tissues. Direct binding studies with 3H-cytochalasin B showed that GLUT density was elevated 20-fold in LX-1 tumors. Immunohistochemically in all tumors, the expression of GLUT-1 was highest in the necrotic/ perinecrotic foci and similar in cells not adjacent to necrotic foci. As the retention of 3H-2-DG was similar in all tumors, these data suggest that the GLUT-1 in perinecrotic tumor cells were not rate limiting for 3H-2-DG uptake. Kidney, liver, and lung had high GP activity and rapid clearance of 3H-2-DG. Sodium orthovanadate (5 mumol), a GP inhibitor, increased the concentration of 3H-2-DG in these tissues, suggesting that GP is a rate-limiting enzyme for 3H-2-DG clearance. All tumor homogenates had low GP activity, and hexokinase activity was not elevated compared to normal tissues. Thus, in the tumors studied, the selective accumulation of 3H-2-DG consistently occurred in the absence of significant GP activity without the marked overexpression of hexokinase or GLUT.
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PMID:The interaction among glucose transport, hexokinase, and glucose-6-phosphatase with respect to 3H-2-deoxyglucose retention in murine tumor models. 883 12

Porphyrins, in combination with light, offer an alternate approach to the treatment of cancer, in the form of photodynamic therapy (PDT). With a view to locate new porphyrins for use in PDT, we evaluated the ability of a novel water-soluble porphyrin, meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin (T4CPP) to induce photodamage in membranes, using rat hepatic microsomes as a model system. Hepatic microsomes treated with T4CPP and exposed to visible light showed significant lipid peroxidation, as assessed by the formation of conjugated dienes, lipid hydroperoxides, and thiobarbituric acid-reactive substances. The peroxidation induced was both time- and concentration-dependent. T4CPP plus light also resulted in the destruction of the microsomal enzymes adenosine triphosphatase and glucose-6-phosphatase. Analysis of the products of peroxidation and selective inhibition by specific inhibitors showed that the oxidative damage induced was mainly due to singlet oxygen and partly due to hydroxyl radical. The porphyrin T4CPP was efficiently labeled with 99mTc. When this 99mTc-labeled porphyrin was injected into a mammary-tumor-bearing rat, it accumulated in the tumor. Our studies suggest that T4CPP, due to its potential to localize in tumors and to induce membrane damage as exemplified by alteration in rat liver microsomes, may have possible applications in this new modality of cancer treatment.
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PMID:Photodynamic effects induced by meso-tetrakis[4-(carboxymethyleneoxy)phenyl]porphyrin using rat hepatic microsomes as model membranes. 905 55

Although 1,25-dihydroxyvitamin D3 has been shown to promote the differentiation of cancer cells and cell lines in vitro, its protective effect against a chemical insult known to induce neoplastic growth in vivo has not been evaluated. The aim of this study was to investigate, in vivo, the influence of the vitamin D status on the early response to an insult known to induce morphological and functional changes leading to hepatocarcinogenesis. The influence of vitamin D status on the susceptibility of rat liver to carcinogenesis was studied after the administration of diethylnitrosamine and 2-acetylaminofluorene, in association with a partial hepatectomy (Solt-Farber protocol), to normal or vitamin D-depleted rats. Preneoplastic foci (gamma-glutamyltranspeptidase-positive and glucose-6-phosphatase-negative) appeared in both groups of animals as early as 1 week after 2-acetylaminofluorene withdrawal and continued to increase during the subsequent weeks. Livers from vitamin D-depleted rats exhibited a significant increase in the number of foci over that observed in normal rats at weeks 1 and 5 after 2-acetylaminofluorene withdrawal. However, the main effect of vitamin D depletion was on focus size, which was found to be significantly greater in vitamin D-depleted rat livers at weeks 2 to 6; focus area (volume fraction) was also found to be consistently larger in livers of vitamin D-depleted rats than in those of normal rats. Labeling of oval cells, a cell compartment possibly associated with the repopulation of the liver parenchyma, was significantly reduced by vitamin D depletion. Control rat livers of both groups showed normal liver histology, and no foci, nodules or oval cells were detected in either group. The present data suggest that vitamin D depletion leads to increased in vivo susceptibility to chemicals known to induce hepatocarcinogenesis. Long-term studies must be conducted to evaluate the effect of vitamin D status on the evolution of preneoplastic foci into frank hepatocellular carcinoma.
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PMID:Influence of the vitamin D status on the early hepatic response to carcinogen exposure in rats. 910 32

Mice bearing interleukin-6 (IL-6)-secreting tumor were used to study the chronic effect of IL-6 on carbohydrate metabolism. Mice were injected with allogeneic tumor cells transduced with the murine IL-6 gene. Serum IL-6 levels were correlated exponentially with tumor weight. Secretion of IL-6 from the developed tumors was associated with decreased food consumption, reduced body weight, and reduced blood glucose levels. Insulin levels did not change, and 2-deoxyglucose uptake was not affected in most tissues examined. A significant increase of 2-deoxyglucose uptake was measured in the liver. Glycogen content in the liver determined 0, 6, 12, and 18 days after tumor inoculation was 42, 23, 12, and 3 mg/g, respectively. The activity of phosphoenolpyruvate carboxykinase was not affected. The activity of glucose-6-phosphatase (G-6-Phase) determined 6, 12, and 18 days after tumor injection was 84, 70, and 50% of G-6-Pase activity in pair-fed mice bearing nonsecreting tumors, respectively. G-6-Pase mRNA levels were markedly reduced due to inhibition of G-6-Pase gene transcriptional rate.
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PMID:Interleukin-6 secretion in mice is associated with reduced glucose-6-phosphatase and liver glycogen levels. 927 78

The levels of iron, zinc, and calcium in liver as well as serum, together with the enzymatic activities of gamma-glutamyl transferase (GGT, EC 2.3.2.2) and glucose-6-phosphatase (G-6-Pase, EC 3.1.3.9) in liver, were critically monitored over various periods in male Swiss albino mice bearing Dalton's lymphoma (DL), a transplantable ascites-producing tumor. Both hepatic and serum contents of iron, zinc, and calcium were found to be maximally elevated (p < 0.001) on day 15 after tumor transplantation as compared with their contents in normal animals. There was a gradual increase in the activity of GGT in liver in lymphoma-bearing mice in comparison with their normal counterparts, which showed a maximum peak (p < 0.001) on day 15, followed by a continuous and sharp fall. Hepatic G-6-Pase activity was found to decrease continuously throughout the progression of lymphoma as compared with its levels to normal animals. Tumor-cell counts in peritoneal lymph fluids of mice containing DL yielded a maximum count of 155.7 x 10(3) cells/mm3 on day 15. A significant correlation was observed among the levels of different metals, enzymatic activities, and tumor-cell counts at different periods of study. From these results, it can be concluded that the metals studied may have a role in initiating and controlling cellular proliferations, through their effects on modulating the activities of the possibly preneoplastic and neoplastic marker enzymes named above.
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PMID:Alterations in total iron, zinc, and calcium levels and their influence on the hepatic activities of gamma-glutamyl transferase and glucose-6-phosphatase in the host bearing transplantable murine lymphoma. 958 38

Preneoplastic liver foci and neoplasms of different morphological phenotypes were induced in rats with N-nitrosomorpholine (NNM; 120 mg/l in drinking water for 7 weeks) and the peroxisome proliferator dehydroepiandrosterone (DHEA; 0.6% in the diet for up to 84 weeks). Preneoplastic glycogen storage foci (GSF) occurred mainly upon treatment with NNM, and amphophilic cell foci (APF) were mainly observed in rats treated with DHEA alone or in combination with NNM. The 2 types of lesions belong to 2 different cellular lineages, the glycogenotic/basophilic lineage and the amphophilic lineage, which are characterized by distinct patterns of alterations in key enzymes of energy metabolism. Whereas in GSF enzymes of glucose metabolizing pathways were modified (increase in glucose-6-phosphate dehydrogenase and pyruvate kinase, decrease in glucose-6-phosphatase), APF mainly demonstrated alterations in mitochondrial enzymes (increase in cytochrome c oxidase, succinate dehydrogenase and glycerol-3-phosphate dehydrogenase) and, to a lower extent, in peroxisomal enzymes (increase in peroxisomal hydratase and acyl-CoA oxidase). The alterations in enzyme expression reflect an insulinomimetic effect in GSF and a thyromimetic effect in APF. Neoplasms resulting from APF show a more differentiated phenotype than those arising from GSF. We suggest that the different and in many aspects opposite effects of the 2 carcinogens on key enzymes of distinct pathways of energy metabolism modulate the process of neoplastic liver cell transformation and result in phenotypically different preneoplasias and neoplasias reflecting different cellular lineages.
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PMID:Differential expression of key enzymes of energy metabolism in preneoplastic and neoplastic rat liver lesions induced by N-nitrosomorpholine and dehydroepiandrosterone. 964 43

Hepatic microsomal glucose-6-phosphatase is a multicomponent system composed of substrate/product translocases and a catalytic subunit. Previously we (Foster et al. (1996) Biochim. Biophys. Acta 12, 244-254) demonstrated that N-bromoacetylethanolamine phosphate (BAEP) is a time-dependent, irreversible inhibitor of glucose-6-phosphate hydrolysis in intact but not disrupted microsomes. We proposed that BAEP manifests its inhibitory effect by binding with a glucose-6-phosphate translocase protein of the glucose-6-phosphatase system. Here we provide additional evidence that BAEP inhibits glucose-6-phosphate transport in microsomal vesicles and utilize [(32)P]BAEP as an affinity label in the identification of a glucose-6-phosphate transport protein. In this study, we identify 51-kDa rat and mouse liver microsomal proteins involved in glucose-6-phosphate transport into and out of microsomal vesicles by utilizing (1) an Ehrlich ascites tumor-bearing mouse model, which displays a decreased sensitivity to the time-dependent inhibitory effect of BAEP, and (2) another glucose-6-phosphate translocase inhibitor, tosyl-lysine chloromethyl ketone, in conjunction with [(32)P]BAEP as an affinity label.
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PMID:N-Bromoacetylethanolamine phosphate as a probe for the identification of a liver microsomal glucose-6-phosphate transporter peptide in rats and Ehrlich ascites tumor-bearing mice. 1077 49

Mice deficient for connexin32 (Cx32), the major gap junction forming protein in liver, are highly susceptible to hepatocarcinogenesis. Because the Cx32 gene is located on the X-chromosome, heterozygous females show mosaicism with respect to Cx32 expression; this enables their use in studying the effect of Cx32-deficiency in a mixed Cx32-plus/Cx32-minus environment in vivo. Female C3H/He mice (Cx32(+/+)) were crossed with Cx32-deficient C57BL/129Sv males (Cx32(Y/-)) to yield F1 females heterozygous with respect to Cx32 (Cx32(+/-)). Patches of hepatocytes were observed in normal liver that either expressed Cx32 or failed to express the protein. The mean fraction of Cx32-negative tissue in liver was about 60% and did not change significantly with age of mice. Neoplastic liver lesions, induced in weanling mice, were identified in serial liver sections by their deficiency in glucose-6-phosphatase staining. Parallel sections were used for immunohistochemical demonstration of Cx32 protein. Smaller lesions were either homogenously Cx32-negative or showed unchanged to slightly elevated levels of Cx32 protein. There were no major differences in number and size distribution between lesions of these 2 phenotypes. In addition, larger lesions were mostly Cx32-negative but often contained embedded patches of Cx32-positive cells. Staining for the proliferation-associated nuclear antigen Ki-67 did not reveal significant differences between Cx32-negative and Cx32-positive hepatocytes in Cx32-mosaic tumors. This suggests that expression of Cx32 within a subpopulation of tumor cells does not negatively regulate their growth nor does it seem to affect the proliferation of their directly neighboring Cx32-negative counterparts.
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PMID:Hepatocarcinogenesis in female mice with mosaic expression of connexin32. 1096 Apr 41

Connexin32 (Cx32) is the major gap junction forming protein in liver. We have recently shown that hepatocarcinogenesis is strongly enhanced in mice deficient in Cx32, demonstrating that lack of functional Cx32 accelerates liver tumorigenesis. Many tumor-promoting agents, including phenobarbital, block gap junctional intercellular communication in vitro, and it has been suggested that this effect is relevant for clonal expansion of neoplastic cells in vivo. We have now tested this hypothesis by analyzing the potency of phenobarbital as a liver tumor promoter in male Cx32-wild-type (Cx32(Y/+)) and Cx32-null (Cx32(Y/-)) mice. Preneoplastic and neoplastic liver lesions were induced in 6-week-old male mice by a single injection of 90 microg/g body weight of N-nitrosodiethylamine, and groups of mice were subsequently kept on phenobarbital-containing (0.05%) or control diet for 39 weeks. Frozen liver sections were prepared, and (pre)neoplastic lesions were identified by their deficiency in glucose-6-phosphatase staining. In addition, the number and size of macroscopically visible tumors were monitored. Phenobarbital led to a approximately 5-fold increase in the volume fraction occupied by glucose-6-phosphatase-deficient liver lesions in Cx32(Y/+) mice, whereas there was no such increase in Cx32(Y/-) mice. Even more pronounced differences were observed with respect to tumor response. Whereas phenobarbital clearly promoted the occurrence of numerous large hepatomas in Cx32(Y/+) mice, no such effect was seen in Cx32(Y/-) mice. These results demonstrate, for the first time, that functional Cx32 protein is required for tumor promotion by phenobarbital.
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PMID:Lack of phenobarbital-mediated promotion of hepatocarcinogenesis in connexin32-null mice. 1101 33


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