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Query: UNIPROT:P06889 (Mol)
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The cellular origin of estrogen-induced kidney tumors in male Syrian hamsters has been repeatedly the subject of controversy. Several authors have proposed that the tumors arise from proximal tubules, from a combination of tubular and interstitial stromal cells, or solely from interstitial cells. Because of the model character of this tumor for hormone-associated cancer, it was further investigated in this study with respect to morphology, enzyme and intermediate filament pattern, the expression of alpha-smooth muscle actin and the extracellular matrix proteins fibronectin and tenascin. These analyses were carried out with early and late tumors as well as metastases to determine possible changes in expression of biochemical parameters during the development and progression of this neoplasm. The enzyme histochemical and intermediate filament patterns were usually the same as those described previously for proliferative foci and early tumors, i.e. highly elevated activities of glucose-6-phosphate dehydrogenase, adenylate cyclase and alkaline phosphatase, a lack of glucose-6-phosphatase and gamma-glutamyltransferase and coexpression of vimentin and desmin, alpha-smooth muscle actin could not be detected in early lesions. In five of 24 advanced tumors inclusions of kidney tubules were found which showed various degrees of alteration in their morphology and enzyme histochemical pattern, but were often directly connected with tubular segments of normal appearance outside the tumor. Like the normal tubules, the enclosed tubular segments were strongly positive for cytokeratin but never expressed vimentin or desmin. Among the 24 tumors studied, two contained cysts which expressed cytokeratin and sometimes also vimentin but not desmin. The enzyme histochemistry of the cells lining the cysts was similar to that of the surrounding tumor mass, except adenylate cyclase was lacking and alkaline phosphatase was not uniformly distributed. In tumors containing cytokeratin-positive cysts, there often were cytokeratin-positive, vimentin-negative and desmin-negative tumor formations in close contact to these cysts. With the exception of cyst formation, the pattern of metastases were identical to that of the primary tumors. All large tumors and the main component of the metastases expressed vimentin, desmin and fibronectin. Mesothelia surrounding metastatic tumor complexes were positive for vimentin, desmin, alpha-smooth muscle actin, fibronectin, cytokeratin and tenascin. It was concluded from these and previous observations on early stages of tumor development that the estrogen-induced hamster kidney tumor originates from mesenchymal interstitial cells (probably pericytes) which may rarely acquire an epithelial phenotype by metaplastic transformation during tumor progression.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Changes in the cellular phenotype and extracellular matrix during progression of estrogen-induced mesenchymal kidney tumors in Syrian hamsters. 171 81

Glucose-6-phosphatase activity was measured in rat liver or pancreatic islet crude homogenates and microsomes. The data recorded in the liver were comparable to those reported in prior studies. However, in the islets, the hydrolysis of D-glucose 6-phosphate by disrupted microsomes represented, when expressed relative to the protein content, less than 2% of the value recorded in liver microsomes. Moreover, no phosphotransferase activity was detected in the islets. These findings impose reservation on both the presence of glucose-6-phosphatase in rat islets and its participation to stimulus-secretion coupling.
Mol Cell Biochem 1991 Feb 27
PMID:Hexose metabolism in pancreatic islets: the glucose-6-phosphatase riddle. 184 30

The uptake of L-[14C]glycine and the activities of intracellular marker enzymes of enterocytes were studied in ligated small intestinal segments of rabbits during experimental cholera induced by intra-intestinal injection of pure cholera toxin (CT). No significant difference was observed in the active uptake of L-[14C]glycine between the CT-injected small intestinal segments and the saline-injected control segments, indicating that there is an intact active transport system for intestinal absorption of L-[14C]glycine during experimental cholera in rabbits. Apart from a significant increase in the activity of a brush border marker enzyme (alkaline phosphatase), there was no significant difference between the activities of marker enzymes for lysosomes (acid phosphate), microsomes (glucose-6-phosphatase), mitochondria (succinate dehydrogenase), and a cytosol enzyme (proteinase) in mucosal homogenates of CT-injected small intestinal segments compared to controls. The finding of an intact mitochondrial marker enzyme together with intact L-[14C]glycine absorption provides a scientific basis for considering the use of glycine and other monoamino monocarboxylic amino acids in "improved" oral rehydration solutions for the treatment of acute diarrhea, including cholera.
Mol Biol Med 1991 Feb
PMID:Effect of cholera toxin on L-[14C]glycine uptake and intestinal cell enzymes in rabbit. 194 84

The neurochemical changes induced by malathion, an organophosphate compound, were determined in rats. Maximal changes were found in the brain 2 h after the administration of malathion in a dose of 500 mg/kg ip. The activities of cholinesterase and succinic dehydrogenase were reduced whereas those of glycogen phosphorylase, phosphoglucomutase, and hexokinase were increased; the lactate content of brain was also increase. In malathion treated adrenalectomized animals, changes in the activities of cerebral cholinesterase and succinic dehydrogenase were still present; other changes were, however, abolished by adrenalectomy. Activities of certain enzymes, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase were not significantly altered by malathion in normal or adrenalectomized animals. The results indicate that cerebral cholinergic mechanism in malathion treated animals was not modified by adrenalectomy which, however, abolished or reduced changes in the activities of certain glycolytic and glycogenolytic enzymes that are involved in the utilization or metabolism of glucose. The brain lactate content in malathion treated adrenalectomized animals was, also, not significantly different from the control values, suggesting that modification of induced changes by adrenalectomy.
Mol Chem Neuropathol
PMID:Modification of malathion induced neurochemical changes by adrenalectomy in rats. 209 80

The frog liver microsome glucose-6-phosphatase activity shows seasonal rhythm, being significatively higher in the winter than in summer. The latency and the sensibility to anionic detergent Deoxycholate is higher in the summer than in winter. During the summer a Km and epsilon Vmax decrease is observed.
Cell Mol Biol 1990
PMID:Frog liver glucose-6-phosphatase activity: seasonal variations of latency and kinetic parameters. 216 62

Experimental infection of golden hamsters with the hookworm, Ancylostoma ceylanicum, caused a profound decline in the hepatic microsomal cytochrome P450 content. Concomitant decrease was also noticed in aminopyrine N-demethylase and benzo[a]pyrene hydroxylase activities. However, aniline hydroxylase activity was only marginally elevated during the infection. Microsomal markers, viz., cytochrome b5, NADH-cytochrome-c reductase, and glucose-6-phosphatase, were not significantly altered. Hepatic tissue exhibited an accumulation of lipids, especially phospholipids, triglycerides, and cholesterol, resulting in fatty necrosis around the central vein region. Isolated hepatic microsomes showed a decrease in phosphatidylcholine content. Impairment in hepatic mixed function oxidase (MFO) activities was further confirmed by prolongation in hexobarbital sleeping time and zoxazolamine-induced paralysis. The hepatic MFO system of A. ceylanicum-infected hamsters responded qualitatively and quantitatively in a manner similar to that of control hamsters, upon stimulation with selective chemical inducers like phenobarbitone and 3-methylcholanthrene. Kinetic and in vitro substrate binding studies revealed that for aminopyrine the substrate affinity and the maximum enzyme activity (Vmax) were decreased, while for aniline the binding affinity was decreased and the binding capacity was enhanced. Results indicate specific/selective impairment of the hepatic microsomal cytochrome P450 system during hookworm infection and may have many practical implications in toxicology and pharmacology.
Exp Mol Pathol 1990 Jun
PMID:Hepatic microsomal cytochrome P450 system during experimental hookworm infection. 236 36

We previously reported that phenylmethylsulfonyl fluoride (PMSF) administration to rats (100 mg/kg, ip in olive oil) as late as 6 or 10 hr after CCl4 (1 ml/kg, ip as a 20% v/v solution in olive oil) can partially prevent the necrogenic response to the hepatotoxin at 24 hr. Here we confirm that observation by electron microscopy and provide further evidence that only in these circumstances were nuclear clumping of chromatin, slight dilatation of the endoplasmic reticulum, myelin figures and lipid droplets in the cytoplasm, large numbers of lysosomes and peroxisomes, glycogen, and slightly swollen mitochondria observable in the protected animals. A very minor part of the late protective effects of PMSF might be due to the effects of this drug on decreasing the intensity of covalent binding of CCl4-reactive metabolites or the intensity of CCl4-induced lipid peroxidation still occurring 6 or 10 hr after CCl4. PMSF administration did not prevent CCl4-induced decreases in cytochrome P450 content or glucose-6-phosphatase activity but partially prevented CCl4-induced calcium accumulation in liver. PMSF treatment increased glutathione and glycogen content in CCl4-poisoned animals, but did not markedly modify protein/phospholipid synthesis or degradation processes. Results suggest that the late protective effects of PMSF administration in CCl4-induced liver necrosis might be due to a favorable modulation of the calcium-calmodulin system similar to that previously described for other drugs.
Exp Mol Pathol 1989 Apr
PMID:Further studies on the mechanism of the late protective effects of phenylmethylsulfonyl fluoride on carbon tetrachloride-induced liver necrosis. 254 23

To determine the cytochemical localization of glucose-6-phosphatase in the human hepatocyte, lead - based and cerium - based media were used. By studying the effects of systematic variation of the incubation medium components, the optimal experimental conditions were determined. The exclusive localization of the cytochemical reaction in the endoplasmic reticulum and nuclear envelope, together with the results of control experiments ensured that these findings could be correlated with the phosphohydrolase activity of the multicomponent glucose-6-phosphatase system.
Cell Mol Biol 1989
PMID:Cytochemical demonstration of glucose-6-phosphatase in human liver. 255 1

In a stop-experiment using the hepatocarcinogen N-nitrosomorpholine, as well as glycogenotic and related lesions, hepatocellular foci with a different histochemical pattern were identified. The outstanding features of these hepatic foci, which may progress to hepatocellular adenoma, were increased activities of mitochondrial glycerol-3-phosphate dehydrogenase (mG3PD), glycogen synthase, pyruvate kinase and glucose-6-phosphatase detected by enzyme histochemistry. Since no decrease in activity of any of the enzymes examined were seen in these foci, compared with normal liver, the term enzymatically hyperactive focus (EHF) is proposed for this type of lesion. Only at the stage of overtly nodular growth did these lesions exhibit some of the characteristic changes seen in nodules developing from glycogenotic foci, namely elevated activities of glucose-6-phosphate dehydrogenase, gamma-glutamyl transferase and glutathione-S-transferase P as well as decreased activities of adenosine-triphosphatase, glucose-6-phosphatase and adenylate cyclase. Some of these enzymes have been used widely in morphometric studies as markers for preneoplastic and neoplastic lesions. The inability to detect early EHF may lead to an underestimation of preneoplastic liver lesions in quantitative studies. Although there are apparent differences in the histochemical patterns of glycogen storing foci and early EHF, these differences tend to disappear during progression to overtly neoplastic lesions. In studies comparing the phenotypic alterations in different types of preneoplastic hepatic lesions, the recognition of EHF may contribute to the distinction of obligatory from facultative phenomena during transformation.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Unusual histochemical pattern in preneoplastic hepatic foci characterized by hyperactivity of several enzymes. 256 54

Liver tumors of the B6C3F1 mouse frequently contain mutations at specific sites of codon 61 of the Ha-ras proto-oncogene. To address whether these mutations occur early or late during carcinogenesis, we analyzed mutations in the Ha-ras gene in small precancerous liver lesions of the B6C3F1 mouse. For this purpose, 10-microns frozen liver sections were prepared and stained for glucose-6-phosphatase activity. Using punching cannuli, we then took small tissue samples of approximately 5-30 micrograms from enzyme-deficient liver lesions and from normal parts of the liver. These tissue samples were analyzed for mutations in the Ha-ras gene by in vitro amplification of DNA via the polymerase chain reaction combined with selective oligonucleotide hybridization. By this approach we were able to analyze mutations in the Ha-ras gene within lesions with diameters of less than 0.5 mm. Our results demonstrate that approximately 15% of the glucose-6-phosphatase-negative lesions that occurred 24-28 wk after a single injection of diethylnitrosamine contain either C----A transversions at the first base or A----G transitions and A----T transversions at the second base of codon 61 of the Ha-ras gene. The same types of mutations, although with a somewhat higher frequency (33%), were found in liver tumors taken 68 wk after diethylnitrosamine treatment. These findings demonstrate that Ha-ras mutations can be detected even in very small precancerous liver lesions, suggesting that these mutations may be an early, perhaps even the first, critical event during murine hepatocarcinogenesis.
Mol Carcinog 1989
PMID:Mutations at codon 61 of the Ha-ras proto-oncogene in precancerous liver lesions of the B6C3F1 mouse. 267 1


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