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:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The drug-metabolizing enzymes of olfactory and respiratory epithelium of cattle were determined. The data of nasal tissues were compared to those of bovine liver. Both oxidative and nonoxidative enzyme activities were investigated. Many compounds including testosterone were used as substrates for the P450-dependent monooxygenase activities. The results demonstrated that the P450 content and all the activities assayed including reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase were much higher in the olfactory than in the respiratory mucosa and for some activities (hexamethyl-phosphoramide and dimethylnitrosamine N-demethylase, aniline hydroxylase, and ethoxycoumarin O-deethylase) the values in the olfactory tissue were even markedly higher than those of liver. Also the activities of some nonoxidative enzymes such as glutathione S-transferase, uridine 5'-diphosphate (UDP)-glucuronyl-transferase, and epoxide hydrolase were higher in the olfactory than in the respiratory mucosa but lower than in liver. The results taken together suggest that the olfactory and respiratory epithelium of cattle, which contain in addition to a wide array of nonoxidative enzymes multiple forms of P450, can be useful and easily available tissues to study the biotransformation processes of odorants.
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PMID:Drug-metabolizing enzymes in liver, olfactory, and respiratory epithelium of cattle. 194 98

The cellular expression of alpha, mu, and pi classes of glutathione S-transferases (GSTs) was investigated in human nasal mucosa by means of immunocytochemical techniques. In the olfactory mucosa, immunoreactivity for GST-alpha was most intense in the acinar cells of the Bowman's glands, with weak immunoreactivity in the supranuclear region of sustentacular cells. Whereas GST-pi was localized only in the sustentacular cells, no GST-mu was detected. In the respiratory mucosa, GST-alpha and GST-pi were detected at the brush borders of ciliated columnar epithelial cells. There were age- and gender-related trends in the expression of GST-alpha, but not GST-pi, in the olfactory mucosa. The intensity of immunoreactivity in the olfactory mucosa was decreased in older subjects. The expression of GST-alpha in the olfactory mucosa of females consistently exhibited greater intensity than that of males at all the ages studied. These differences were not observed in the respiratory mucosa. These results indicate that acinar cells of the Bowman's glands and sustentacular cells are the major sites of phase II biotransformation in the human nasal mucosa.
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PMID:Age- and gender-related trends in the expression of glutathione S-transferases in human nasal mucosa. 757 61

Many xenobiotics induce lesions within the nasal cavity of experimental animals which are site specific. This site selectivity may be due to regional deposition within the nasal cavity and/or the localisation of biotransformation enzymes. We have developed methodology which allows immunohistochemical localisation of xenobiotic biotransformation enzymes in transverse sections of the rat nasal cavity identical to those normally taken for pathological examination. We report the application of this methodology to six isoenzymes of the glutathione S-transferases (GSTs). All six isoenzymes were predominantly located within olfactory epithelium covering the ethmoturbinates (levels III and IV) and extending forwards into the dorsal meatus (level II). Squamous and transitional epithelia showed little or no staining while respiratory epithelium was weakly stained. Within the respiratory epithelium only the ciliated columnar cells and, to a lesser extent, some of the seromucous glands contained GSTs. Within olfactory epithelium the sustentacular cells, basal cells and subepithelial glands all stained positive for GSTs. The different cell types of olfactory epithelium preferentially express different GST isoenzymes: 1-1 and 2-2 were predominantly located in the subepithelial glands; 3-3, 4-4 and 8-8 in sustentacular and basal cells; 7-7 in basal cells.
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PMID:Immunohistochemical localisation of six glutathione S-transferases within the nasal cavity of the rat. 771 67

Anthraquinone dyes are utilized by the military in colored-smoke grenades. During production, workers in munitions plants may be exposed to fugitive emissions of these dyes or mixtures thereof. The effects of a prototype violet dye mixture (VDM) consisting of Disperse Red 11 (DR11), [1,4-diamino-2-methoxy-anthraquinone] and Disperse Blue 3 (DB3) [1-methylamino-4-hydroxyethylamino-anthraquinone] on F344 male and female rats have been investigated. Acute 1-day inhalation exposures (6 hr) to VDM were conducted at 1000, 300, 100, 70, 40, and 10 mg/m3, with an additional exposure to 40 mg/m3 6 hr/day for 5 days; 4.22 +/- 2.1 microns (MMAD +/- delta g). Lung burdens of dye, general histopathology, and/or liver function were evaluated at 0, 3, and 7 days postexposure. Unexpected lethality due to severe liver damage was observed with acute exposures of > or = 300 mg/m3 and in the 5-day 40 mg/m3 exposures. Centrilobular degeneration and necrosis of liver cells was concentration-dependent with inhalation of VDM > or = 40 mg/m3. In addition, nasal olfactory epithelium exhibited degeneration and necrosis with acute exposures > or = 10 mg/m3. Lung instillations at 250, 500, and 1000 micrograms of the VDM revealed no lung or liver toxicity. Because per os exposure due to preening was suspected as a major exposure route, a gavage study with the VDM and its two component dyes DR11 and DB3 (800 mg/kg) was undertaken. One day following gavage with DR11 or DB3, serum enzymes indicative of liver toxicity (LDH, SGPT, SDH, and ICDH) were slightly elevated (1-6x control). However, rats gavaged with VDM had serum enzyme levels 10-100x control by Day 1 after gavage, indicating acute liver toxicity. Activities of liver enzymes involved in xenobiotic and glutathione metabolism were also acutely affected. All of the dyes caused various degrees of induction of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and nonprotein sulfhydryls. The enzymes involved in xenobiotic metabolism (glutathione S-transferase, NADPH cytochrome-c reductase, and P450) were also elevated by the two component dyes, in contrast to their significant depression with VDM treatment. The similarity between the liver and olfactory epithelium effects of these compounds and the lack of pulmonary tissue effects is not fully understood, but the interaction of the individual dyes as VDM emphasizes the need to assess chemicals such as the anthraquinones as their likely-to-be-encountered mixtures.
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PMID:Toxicity of an anthraquinone violet dye mixture following inhalation exposure, intratracheal instillation, or gavage. 812 3

The expression of three classes of glutathione S-transferases (GSTs), Alpha, Mu, and Pi was investigated in the nasal mucosae of rats during development using immunohistochemical methods. GST Alpha and Mu were first detected in the supranuclear region of sustentacular cells on embryonic days 16. The Bowman's glands expressed differential patterns of immunoreactivity during development, beginning at postnatal day (P) 2 and P6 for Alpha and Mu classes, respectively and being greatest at P11 for both. The acinar cells of vomeronasal glands in the vomeronasal organ expressed Alpha and Mu classes of GSTs from P11 onwards. In the septal organ of Masera, the supranuclear region of sustentacular cells expressed GSTs from P11 with little or no variation during development. In the respiratory mucosa, Alpha and Mu classes of GSTs were detected at the brush borders of ciliated cells and in the acinar cells of posterior septal glands, but not in anterior septal or respiratory glands located on the turbinates. Compared to olfactory mucosa, the changes in immunoreactivity for GSTs were less pronounced in the respiratory mucosa during development. Specific GST Pi immunoreactivity was not detected in the nasal mucosae at any stage of development studied. The occurrence of GSTs in the nasal mucosa, including olfactory, vomeronasal, septal, and respiratory epithelia, suggests that the GSTs are actively involved in the biotransformation of xenobiotics including odorants and pheromones, and may also participate in perireceptor processes such as odorant clearance. In addition, we have developed a working model describing the cellular localization of certain phase I (e.g., cytochrome P-450s) and phase II (e.g., GSTs, gamma-glutamyl transpeptidase) biotransformation enzymes in the olfactory mucosa and their proposed roles in xenobiotic metabolism.
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PMID:Differential expression of alpha, mu, and pi classes of glutathione S-transferases in chemosensory mucosae of rats during development. 813 95

Glutathione transferase (GST) was investigated in the olfactory and respiratory epithelium of cattle. A significantly more abundant GST in terms of either protein amount or activity was found in the olfactory rather than in the respiratory epithelium. No apparent qualitative differences in the isoelectric focusing, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and HPLC profiles were noted in the reduced glutathione (GSH) affinity purified GST pool of olfactory and respiratory epithelium. Both tissues have at least six GST isoenzymes with isoelectric point values of 4.9 (peak I), 5.3 (peak II), 5.95 (peak III), 6.5 (peak IV), 7.1 (peak V) and 9.3 (peak VI). From both tissues at least seven different GST subunits can be resolved by HPLC analysis. The GST isoenzymes having pI at 5.3 and 9.3 were predominantly expressed in the olfactory than in the respiratory epithelium. These latter forms conjugate GSH efficiently with alkenals and hydroperoxides, respectively. Kinetic, immunological and structural properties, including HPLC analysis and N-terminal region amino acid sequence seem to indicate that the bovine nasal mucosa tissue in addition to a GST subunit which is orthologue to rat subunit 8 (alpha class) express tissues specific subunits.
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PMID:Glutathione transferase isoenzymes in olfactory and respiratory epithelium of cattle. 827 45

Olfaction is mediated by G protein-coupled receptors. In isolated rat olfactory cilia, odorants such as citralva stimulate a burst of cAMP, which peaks in 50 ms and returns almost to base-line level within 150 ms in the continuing presence of odorant. This desensitization is mediated by the cAMP dependent protein kinase and a specialized G protein-coupled receptor kinase originally termed beta ARK2 (GRK3). In vitro experiments suggest that the prenylated beta gamma-subunits of heterotrimeric G proteins target the cytosolic beta ARK1 (GRK2) enzyme to its membrane bound receptor substrate by binding to sites in its carboxyl terminus. Here we demonstrate that odorants stimulate translocation of GRK3 from cytosol to membranes in isolated rat olfactory cilia. We introduced a glutathione S-transferase-GRK3ct fusion protein, containing the carboxyl-terminal 222 amino acid residues of GRK3, which includes the beta gamma binding site, or a 28-amino acid peptide derived therefrom, into permeabilized cilia preparations. These reagents block odorant-mediated enzyme translocation and desensitization while markedly attenuating odorant-stimulated phosphorylation of olfactory proteins. These findings suggest that beta gamma-subunits may physiologically regulate a G protein-coupled receptor kinase and that enzyme translocation may be a general and required feature of the activity of some members of this enzyme family.
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PMID:Olfactory desensitization requires membrane targeting of receptor kinase mediated by beta gamma-subunits of heterotrimeric G proteins. 827 21

The glutathione S-transferases (GSTs) of rat olfactory epithelium have been characterized with regard to substrate specificity and subunit composition and compared to those of the liver. The presence of cytosolic GST activity in rat olfactory epithelium was confirmed and, using 1-chloro-2,4-dinitrobenzene as substrate, was found to be approximately one-third that of the liver. Olfactory microsomal GST activity was greater than that of liver microsomes and could be activated by treatment with the sulphydryl agent N-ethylmaleimide. The subunit and isoenzyme profile of GSTs in the olfactory epithelium was investigated using a number of techniques. (1) Olfactory GSTs were characterized using a range of relatively subunit-specific substrates. Activities ranged from 40-90% of those found in liver. Most noticeable was the extremely low olfactory activity with the substrate specific for subunit 1. (2) Immunoblotting with antibodies against specific rat hepatic GSTs confirmed the presence of a number of subunits and the absence of subunit 1. (3) F.p.l.c. chromatofocusing and reverse-phase h.p.l.c. indicated that the cytosolic GST profile of olfactory epithelium is unique and is made up of subunits 2, 3, 4, 7, 8 and 11 with subunits 3 and 4 predominating. There is an absence of isoenzymes containing subunit 1.
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PMID:The characterization of glutathione S-transferases from rat olfactory epithelium. 843 89

The olfactory epithelium is exposed to a variety of xenobiotic chemicals, including odorants and airborne toxic compounds. Recently, two novel, highly abundant, olfactory-specific biotransformation enzymes have been identified: cytochrome P-450olf1 and olfactory UDP-glucuronosyltransferase (UGT(olf)). The latter is a phase II biotransformation enzyme which catalyses the glucuronidation of alcohols, thiols, amines and carboxylic acids. Such covalent modification, which markedly affects lipid solubility and agonist potency, may be particularly important in the rapid termination of odorant signals. We report here the identification and characterization of a second olfactory phase II biotransformation enzyme, a glutathione S-transferase (GST). The olfactory epithelial cytosol shows the highest GST activity among the extrahepatic tissues examined. Significantly, olfactory epithelium had an activity 4-7 times higher than in other airway tissues, suggesting a role for this enzyme in chemoreception. The olfactory GST has been affinity-purified to homogeneity, and shown by h.p.l.c. and N-terminal amino acid sequencing to constitute mainly the Yb1 and Yb2 subunits, different from most other tissues that have mixtures of more enzyme classes. The identity of the olfactory enzymes was confirmed by PCR cloning and restriction enzyme analysis. Most importantly, the olfactory GSTs were found to catalyse glutathione conjugation of several odorant classes, including many unsaturated aldehydes and ketones, as well as epoxides. Together with UGT(olf), olfactory GST provides the necessary broad coverage of covalent modification capacity, which may be crucial for the acuity of the olfactory process.
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PMID:Glutathione S-transferases in rat olfactory epithelium: purification, molecular properties and odorant biotransformation. 850 73

Previous studies have shown that the mRNA encoding the Na+/Cl(-)-dependent "orphan" transporter Rxt1 is expressed exclusively in the central nervous system (CNS). In the present study, specific antibodies were raised in rabbits for the detailed mapping of this transporter in the rat. The C-terminal part of Rxt1 was fused with glutathione-S-transferase (Rxt1ct-GST) and the resulting fusion protein was used as antigen. The specificity of the antiserum toward Rxt1 was confirmed by immunofluorescent, Western blot, and immunoautoradiographic experiments. In cerebral cortex membranes, Rxt1-like material recognized by the antiserum is a glycosylated protein of 97-116 kDa. This protein was the most abundant in the caudate-putamen, followed, in decreasing order, by the cerebral cortex approximately hippocampus > cerebellum > brainstem > spinal cord. In contrast, no immunoreactive material could be detected in peripheral tissues (tongue, thymus, heart, lung, spleen, kidney, adrenals, liver, skeletal muscle, intestine, testis). Immunoautoradiographic labeling with affinity-purified anti-Rxt1ct-GST antibodies showed high levels of Rxt1-like material in the olfactory bulb, cerebral cortex, striatal complex, hippocampal formation, superior layer of the anterior colliculus, cortex, and deep nuclei in the cerebellum. The regional distribution of Rxt1-like material generally matched that of GABAergic and glutamatergic projections in agreement with previous in situ hybridization data.
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PMID:Immunolabeling of the Na+/Cl(-)-dependent "orphan" transporter Rxt1 in the rat central nervous system. 858 11


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