Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Established renal epithelial cell lines of human, pig, and dog origin (293, LLC-PK1, MDCK) were examined in terms of nephrotoxicity and ability to biotransform cyclosporine A (CsA). All three cell lines exhibited a comparable concentration dependent cytotoxicity to CsA treatment. Alterations in cell function included a decreased transport of lysine, an inhibition of growth, and an activation of lysosomal and mitochondrial activity as indicated by the increased uptake of neutral red (NR) and increased reduction of the tetrazolium dye MTT at 1-6 microM CsA. Increased leakage of lactic dehydrogenase and activities of gamma-glutamyl transpeptidase (GGT) and N-acetyl-beta-D-hexosaminidase were observed at 48 h and 12 microM CsA. A discrimination between CsA and the less nephrotoxic cyclosporine-(CsH) was shown for DNA synthesis and NR uptake. The contribution of extrarenal parameters on kidney cell function was studied by the addition of medium from hepatocytes exposed to CsA to the kidney cell lines. A more potent inhibition of DNA synthesis and enhanced reduction of MTT resulted than by addition of equimolar CsA directly to the kidney cells. These data indicate that hepatocyte constituents present in the medium due to CsA treatment affect kidney cell function; additionally, the presence of CsA metabolites may contribute to the CsA-induced nephrotoxicity. The vascular nephrotoxicity induced by CsA, an increased deposition of platelets in the renal arterioles, was mimicked by cocultures of endothelial cell monolayers and platelets. CsA increased the aggregability and adherence of platelets to the endothelial cell monolayers, whereas CsH had no effect.
Mol Toxicol
PMID:Cyclosporine A nephrotoxicity studied by the combined application of kidney cell lines, hepatocytes, and endothelial-platelet cocultures. 350 90

Lithium diiodosalicylate (LIS) was used to selectively solubilize proteins from purified intestinal brush border membrane vesicles. Incubation of the vesicles with increasing concentrations of LIS resulted in the progressive release of proteins with total disruption of the membranes being obtained at 200 mM. Maximum selectivity was observed at 20-30 mM LIS which preferentially released actin and other non-glycosylated proteins while all the glycoproteins remained associated with the membrane. Electron micrographs showed that, after LIS treatment, brush border vesicles are partially disrupted and have lost their inner core of microfilaments. Sucrase, trehalase, leucylnaphthylamide hydrolase, gamma-glutamyl transpeptidase and alkaline phosphatase all retained more than 70% of their activities and remained associated with the membrane fraction after LIS solubilization (30 mM). The results indicate that lithium diiodosalicylate treatment provides an efficient method for the separation of cytoskeletal proteins from intrinsic membrane glycoproteins and should be very useful for the purification of microvilli proteins and for the study of membrane-protein interactions.
Mol Cell Biochem 1986 Jun
PMID:Selective release of inner core proteins from intestinal microvillus membrane by lithium diiodosalicylate. 372 49

The gamma-glutamyltransferase (gamma-GT) activity decreased by 50% following adrenalectomy of female rats, in homogenate as well as in a purified plasma membrane preparation from liver. In contrast, such a variation was not found in the kidney. None of 3 other enzyme activities of the plasma membrane, namely 5'-nucleotidase, alkaline phosphatase, and alkaline phosphodiesterase I, was decreased by adrenalectomy. Administration of hydrocortisone (5 mg/100 g body weight) resulted in a 2.6-fold increase in hepatic gamma-GT activity from adrenalectomized rats. The hydrocortisone-mediated stimulation of gamma-GT activity was dose- and time-dependent. The 5'-nucleotidase and leucine aminopeptidase activities were not modified by the hydrocortisone treatment. The activity of gamma-GT was mainly associated with nuclear fractions (nuclei and plasma membranes) obtained from liver homogenates of either control, adrenalectomized or adrenalectomized hydrocortisone-treated animals, and this activity was purified 18-fold in a plasma-membrane preparation as compared to homogenate. These data suggest that adrenalectomy and conversely hydrocortisone treatment modulate specifically the hepatic plasma-membrane gamma-GT activity. This represents one of the first demonstrations of a specific modulation by glucocorticoids of an enzyme activity typical of the plasma membrane.
Mol Cell Endocrinol 1980 May
PMID:In vivo modulation of rat hepatic gamma-glutamyltransferase activity by glucocorticoids. 610 52

Preneoplastic liver foci were produced in female Wistar rats by the administration of 2-acetylaminofluorene (0.03% w/w) in the diet for 174 days. Increased UDP-glucuronyltransferase (UDP-GT) could be visualized immunohistochemically in the same focal areas which were ATPase-negative and gamma-glutamyltranspeptidase-positive. Immunohistochemical detection was possible using rabbit anti-UDP-GT and peroxidase-labeled swine anti-rabbit immunoglobulins. The results of immunohistochemistry were substantiated by enzyme determination in microdissected material. UDP-GT activity was 5-fold higher in focal areas in comparison with the surrounding liver tissue. Increased UDP-GT activity in conjunction with the altered pattern of other drug-metabolizing enzymes is consistent with increased resistance of preneoplastic cells to the cytotoxicity of carcinogens. Immunohistochemical detection of UDP-GT may provide a new marker for preneoplastic lesions which, in conjunction with other markers, may prove useful in analyzing the various stages of liver carcinogenesis and the remodeling of preneoplastic lesions after cessation of carcinogenic stimuli.
Virchows Arch B Cell Pathol Incl Mol Pathol 1983
PMID:Immunohistochemical and biochemical detection of uridine-diphosphate-glucuronyltransferase (UDP-GT) activity in putative preneoplastic liver foci. 613 91

The isolation of renal proximal tubular (PT) cells from the fresh urinary sediment ( UrS ) of familial hypercholesterolemic (FH) homozygotes using discontinuous Ficoll gradient centrifugation was studied. For comparative purposes, cultured cells derived from normal human UrS or kidney were also studied. Unfractionated PT cells were nucleated and 90-99% of the cells excluded trypan blue. Both the unfractionated and fractionated cultured normal PT cells contained numerous empty cytoplasmic vesicles. In contrast, similar preparations from the UrS of FH homozygotes contained membrane-enclosed cytoplasmic vesicles that stained with the Papanicolaou (Pap) reagent and were strongly positive with a fluorescein-labeled antibody against lactosylceramide. The PT cells of FH homozygotes contained 2.0 to 2.5 fold higher activity of gamma-glutamyltransferase and alkaline phosphatase, respectively, than the unfractionated UrS cells. We conclude that human PT cells can be separated from other UrS cells by ficoll gradient centrifugation, and that most, if not all of the LacCer present in the UrS of FH homozygotes is associated with the PT cells. Purified PT cells should provide a useful model to test the biochemical mechanisms of LacCer accumulation in FH.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:Separation of human urinary proximal tubular cells from familial hypercholesterolemic homozygotes by Ficoll gradient centrifugation. Morphological and biochemical characteristics. 614 47

To clarify differences between gamma-glutamyl transpeptidase (gamma GT) expression in the rat and the mouse small intestine, we cloned and sequenced 13 rat small intestine gamma GT cDNAs and compared them with those obtained from the mouse (Carter, et al. (1994) J. Biol. Chem. 269, 24581-24585). We found that all 13 were type VI, which in both species accounts for 80-90% of intestinal gamma GT. However, rat type VI gamma GT is substantially longer than mouse type VI RNA and includes at least 67 additional nucleotides at the 5' end that are non-homologous with the 5' end of the mouse type VI RNA; further, these show no homology to another mouse exon (VII) that splices to type VI RNA. In addition, a 168 nucleotide stretch is present in the middle of rat RNA that is absent in mouse type VI RNA.
Biochem Mol Biol Int 1995 May
PMID:Rat small intestine expresses primarily type VI gamma-glutamyl transpeptidase RNA. 749 70

Polyclonal antibodies were produced against rat kidney gamma-glutamyl transpeptidase (GGT) and against a synthetic peptide corresponding to residues 512-534 in rat GGT. The anti-peptide antibody bound denatured GGT, acivicin-treated GGT and GGT absorbed to microtiter plates, but not GGT in solution, and did not inhibit GGT. The antibody against native GGT inhibited its activity in solution and did not bind efficiently adsorbed GGT in direct ELISA. It was active in direct and competition ELISA using kidney brush border membranes as the adsorbed antigen. The results indicate that these antibodies recognize conformational rather than sequence epitopes in GGT, and that marked changes occur in the conformation of GGT upon its absorption to plates or its reaction with acivicin.
Biochem Mol Biol Int 1994 Jun
PMID:Detection of conformational changes in rat kidney gamma-glutamyl transpeptidase by an antibody against a synthetic peptide belonging to part of the reactive centre of the enzyme. 752 2

Long-Evans Cinnamon (LEC) rats, characterized by a gross accumulation of hepatic Cu and the spontaneous onset of hepatitis, have been established to be an animal model for Wilson disease. They were used to estimate the relationships among copper (Cu), metallothionein (MT), and reduced glutathione (GSH) in biliary excretion in this study. Even though a huge amount of MT existed in the LEC rat liver (5016 micrograms/g liver) compared to that (63 micrograms/g liver) of controls (Fischer rats), the biliary excretion of MT (65 ng/ml bile) did not reflect the accumulated MT level in LEC rats. It seems likely that MT does not excrete intrinsically into the bile. Biliary excretion of Cu (0.17 microgram/ml) in LEC rats was significantly lower than that (0.57 microgram/ml) in Fischer rats. The difference in biliary excretion of GSH between the two groups was significant but slight. The reduced excretion of GSH into bile in LEC rats may be due to increased hepatic gamma-glutamyltransferase but not to hepatic GSH levels. There were no differences in biliary potassium and inorganic phosphorous between the two groups. On the other hand, excretion of lysosomal enzymes such as beta-N-acetylglucosaminidase into bile was much lower in LEC rats (15.6 units/liter) than in controls (42.5 units/liter). The defective biliary excretion of Cu may be due to impaired lysosomal exocytosis, rather than canalicular membrane impairment. The LEC rat is very useful for research into the dynamics of metal excretion via the hepatobiliary system.
Biochem Mol Med 1995 Jun
PMID:Biliary excretion of copper, metallothionein, and glutathione into Long-Evans Cinnamon rats: a convincing animal model for Wilson disease. 755 24

Among the proto-oncogenes examined by northern blot analysis, c-myc, c-Ha-ras, c-fos, and c-raf-1 have been reported to be activated in rat liver cell carcinomas. However, there are relatively few reports on protooncogene expression in altered hepatic foci (AHF) early during hepatocarcinogenesis in the rat. In this study, diethylnitrosamine (DEN) at doses ranging from 10 to 200 mg/kg was used to initiate and phenobarbital (0.05%) to promote AHF in rats. AHF were detected by the presence of the marker enzymes glutathione s-transferase, placental form (GST-P); gamma-glutamyltranspeptidase (GGT); glucose-6-phosphatase (G6Pase); and canalicular adenosine triphosphatase (ATPase). Proto-oncogene expression in individual AHF was investigated by in situ hybridization (ISH). ISH for the mRNAs of c-Ha-ras, c-fos, and c-raf-1 revealed little or no expression in AHF. However, the levels of c-myc mRNA were increased in about 10% of the AHF initiated by the highest dose of DEN (200 mg/kg). Thus, altered expression of proto-oncogenes was not seen in AHF initiated by nonnecrogenic doses of DEN and promoted by phenobarbital. However, at the necrogenic dose of 200 mg/kg DEN, c-myc expression was found mostly in AHF in which abnormal expression of GST-P, GGT, G6Pase, and ATPase was also present, indicating that c-myc expression is correlated with phenotypically greater complexity of the AHF, a characteristic of malignant hepatic neoplasms in the rat.
Mol Carcinog 1995 Nov
PMID:Expression of c-myc in altered hepatic foci induced in rats by various single doses of diethylnitrosamine and promotion by 0.05% phenobarbital. 757 7

The secretion produced by Rathke's glands of Kemp's ridley sea turtles (Lepidochelys kempi) contains the enzyme gamma-glutamyl transpeptidase. The approximately 200 kDa enzyme contains two different subunits, alpha (54 kDa) and beta (21 kDa), in an unknown stoichiometry. The enzyme transfers gamma-Glu from a number of different donors, such as glutamine, glutathione, S-Me-glutathione, N epsilon(gamma-Glu)-Lys, gamma-Glu-Ala, and other gamma-glutamyl amino acids, either to water or to a variety of acceptor substrates. It appears that a free alpha-amino group is the preferred acceptor. The enzyme is not inhibited by typical sulfhydryl reagents such as N-ethyl-maleimide, p-(chloro)mercuri-benzoate or 5,5'-dithio-bis-(2-nitrobenzoate) or by the active Ser reagent tosyl fluoride. Maleate stimulates the activity of the enzyme, and in the presence of 100 mM maleate 2 mM tosyl fluoride becomes an inactivator of the enzyme. The catalytic and molecular properties of the turtle gamma-glutamyl transpeptidase are similar to those established for mammalian gamma-glutamyl transpeptidase. Neither the physiological role of the enzyme nor the biological function of the secretion in which it occurs is understood at this time.
Comp Biochem Physiol B Biochem Mol Biol 1995 Jun
PMID:Characterization of gamma-glutamyl transpeptidase from the Rathke's gland secretions of Kemp's ridley sea turtles (Lepidochelys kempi). 759 89


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