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)

We have used a polyclonal antiserum to bovine ciliary epithelium, a secretory tissue involved in the formation of aqueous humor, to immunoscreen a directional lambda gt11 Sfi-Not cDNA expression library prepared from bovine ciliary epithelium poly(A)+ RNA. After immunoscreening 6 x 10(5) independent clones, 41 cDNA clones positive for ciliary epithelium were isolated and characterized. About one-third of the positive cDNA clones were found to be identical and to encode a glutathione S-transferase (GST) class-pi. The largest bovine GST cDNA clone isolated, pCN11, contains an open reading frame of 630 bases, encoding a protein of 210 amino acids with a calculated molecular weight of 23,335 Da. The corresponding amino acid sequence showed an overall identity of 85.6% with the human, and 85.2% with the rat and mouse GST class-pi. Northern analysis of bovine ocular tissues revealed that the GST class-pi gene encodes a 0.8-kilobase mRNA which is expressed most abundantly in cornea, ciliary epithelium and retina, and in lower levels in iris and lens. Cell lines derived from non-pigmented or pigmented bovine ciliary epithelium also showed high levels of GST-pi mRNA expression. These results provide additional evidence for differential gene expression of GST class-pi mRNA in various areas of the bovine eye.
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PMID:Isolation of a cDNA encoding a glutathione S-transferase (GST) class-pi from the bovine ocular ciliary epithelium. 147 80

Studies were undertaken to investigate the effect of t-butylated hydroxytoluene (BHT) on reduced glutathione (GSH) levels and related enzymes in rat ocular tissues. GSH levels were significantly enhanced when 1 microM BHT was included in the medium of rat lens cultures. BHT had a dose-dependent effect on GSH levels of lenses in cultures. Inclusion of 10 microM BHT in the culture medium resulted in a twofold increase in GSH levels of the lens within 24 hr. Increased gamma-glutamylcysteine synthetase activity concomitant with the increased amount of [35S]methionine incorporation in GSH strongly suggested that BHT caused enhanced levels of GSH in lenses by increasing de novo biosynthesis. A significant increase was also observed in glutathione S-transferase (GST) levels of lenses in culture containing BHT in the medium. Present studies also demonstrated that rat lens expresses only the mu and pi class GST isoenzymes and both these classes of isoenzymes were elevated by BHT. Oral administration of BHT to rats also resulted in enhanced in vivo levels of GSH in lens, retina and cornea. In addition, a significant in vivo increase in the levels of GST, GSH-peroxidase, GSH-reductase, gamma-glutamylcysteine synthetase, and glucose 6-phosphate dehydrogenase was observed in the lens, retina, and cornea of BHT-fed rats.
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PMID:t-butylated hydroxytoluene enhances intracellular levels of glutathione and related enzymes of rat lens in vitro organ culture. 154 39

Studies of others have shown that class 3 aldehyde dehydrogenase is a major component of the epithelial cells of the mammalian cornea. Here we demonstrate by peptide sequencing that other major proteins of the corneal epithelium are also identical or related to enzymes in the human, mouse, kangaroo, chicken, and squid. Aldehyde dehydrogenase class 3 was found to be the major protein of human, mouse, and kangaroo corneal epithelial cells. Peptidyl prolyl cis-trans isomerase (cyclophilin) or a homologue thereof is strikingly abundant in the corneal epithelial cells of chicken, but not mammals, and appears to be absent from the cornea of squid. By contrast, enolase or its homologue is relatively abundant in both the mammalian and chicken corneal epithelial cells. In some instances, abundant enzymes are common to cornea and lens in the same species--for example, arginino-succinate lyase/delta 1-crystallin in the chicken and glutathione S-transferase-like protein in the squid; in other cases, the abundant proteins in the cornea have not been found as lens crystallins in any species--for example, aldehyde dehydrogenase class 3 and cyclophilin. These data suggest that enzymes and certain enzyme-crystallins have been recruited as major corneal proteins in a taxon-specific manner and may serve structural rather than, or as well as, enzymatic roles in corneal epithelial cells.
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PMID:Taxon-specific recruitment of enzymes as major soluble proteins in the corneal epithelium of three mammals, chicken, and squid. 157 Mar 26

To assess the biotransformational capability of ocular tissues in the rabbit, representative phase II enzymes were assayed in five tissues from the eye, and in the liver, kidney, and intestine. Within the eye, the iris/ciliary body exhibited the highest glutathione S-transferase activity, whereas the cornea possessed the highest specific activities for N-acetyl-, sulfo-, and UDP-glucuronosyl-transferases. Cornea, iris/ciliary body, choroid, and retina exhibited significant activities of p-aminobenzoic acid N-acetyltransferase, 2-naphthol sulfotransferase, and 1-chloro-2,4-dinitrobenzene glutathione S-transferase. Despite its size and protein content, lens displayed little or no biotransformational activity. Only the iris/ciliary body conjugated sulfobromophthalein with glutathione. UDP-glucuronsyltransferase activity varied depending on tested substrates and tissues. When compared to liver, kidney, or intestine, N-acetyltransferase activity in the iris/ciliary body nearly matched the rate measured in kidney, glutathione S-transferase activity in cornea and iris/ciliary body was nearly 70 and 89%, respectively, of the rate in intestine, and corneal sulfotransferase activity was greater than that in kidney. These data suggest that biotransformation pathways are present in the eye, and particularly in ocular tissues having adequate blood supply or interfacing with the external environment.
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PMID:Comparative study of phase II biotransformation in rabbit ocular tissues. 168 Jun 41

Five forms of glutathione (GSH) S-transferase (GST) having catalytic activities towards a variety of xenobiotics were present in bovine iris-ciliary body. In contrast to that in lens, cornea, and retina, GST isoenzymes belonging to all the three classes (alpha, mu and pi) were present in iris as well as in the ciliary body. GST isoenzymes of iris-ciliary body had pI values of 8.7, 7.4, 7.0, 6.6, and 6.0. GST 8.7 and GST 7.4 were apparent homodimers of 27,000 and 22,500 Mr subunits, respectively. GST 8.7 cross-reacted only with antibodies raised against the alpha class GST of human liver and GST 7.4 cross-reacted with the antibodies raised against GST pi of human placenta. GST 7.0 and 6.6 were heterodimers of Mr 26,500 and 25,000 subunits and both these subunits cross-reacted with the antibodies raised against the mu class human GST. Iris-ciliary body contained both, GSH peroxidase I and GSH peroxidase II activities and in this respect also, they differ from lens, cornea, and retina each of which have only one of these two activities. The presence of several GST isoenzymes belonging to all the three major classes and both GSH peroxidase I and II activities in iris-ciliary body may be important for the detoxification of oxidants and xenobiotics in order to prevent their infiltration in aqueous humor.
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PMID:Glutathione S-transferase of bovine iris and ciliary body: characterization of isoenzymes. 271 2

Isozyme characterization of glutathione S-transferase (GST) isolated from bovine ocular tissue was undertaken. Two isozymes of lens, GST 7.4 and GST 5.6, were isolated and found to be homodimers of a Mr 23,500 subunit. Amino acid sequence analysis of a 20-residue region of the amino terminus was identical for both isozymes and was identical to GST psi and GST mu of human liver. Antibodies raised against GST psi cross-reacted with both lens isozymes. Although lens GST 5.6 and GST 7.4 demonstrated chemical and immunological relatedness, they were distinctly different as evidenced by their pI and comparative peptide fingerprint. A corneal isozyme, GST 7.2, was also isolated and established to be a homodimer of Mr 24,500 subunits. Sequence analysis of the amino-terminal region indicated it to be about 67% identical with the GST pi isozyme of human placenta. Antibodies raised against GST pi cross-reacted with cornea GST 7.2. Another corneal isozyme, GST 8.7, was found to be homodimer of Mr 27,000 subunits. Sequence analysis revealed it to have a blocked amino-terminus. GST 8.7 immunologically cross-reacted with the antibodies raised against cationic isozymes of human liver indicating it to be of the alpha class. Two isozymes of retina, GST 6.8 and GST 6.3, were isolated and identified to be heterodimers of subunits of Mr 23,500 and 24,500. Amino-terminal sequence analysis gave identical results for both retina GST 6.8 and GST 6.3. The sequence analysis of the Mr 23,500 subunit was identical to that obtained for lens GSTs. Similarly, sequence analysis of the Mr 24,500 subunit was identical to that obtained for the cornea GST 7.2 isozyme. Both the retina isozymes cross-reacted with antibodies raised against human GST psi as well as GST pi. The results of these studies indicated that all three major classes of GST isozymes were expressed in bovine eye but the GST genes were differentially expressed in lens, cornea, and retina. In lens only the mu class of GST was expressed, whereas cornea expressed alpha and pi classes and retina expressed mu and pi classes of GST isozymes.
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PMID:Differential expression of alpha, mu and pi classes of isozymes of glutathione S-transferase in bovine lens, cornea, and retina. 319 Feb 36

Two cationic (pIs 9.1 and 7.6) and one anionic (pI 4.4) forms of glutathione S-transferase have been purified to an apparent homogeneity from human cornea using glutathione-linked affinity chromatography and isoelectric focusing. The substrate specificities of the three enzyme forms are significantly different from each other. None of the three forms of human cornea glutathione S-transferase express glutathione peroxidase II activity. Immunological and structural studies reveal that human cornea enzymes have structural similarities with glutathione S-transferases of other human tissues.
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PMID:Characterization of glutathione S-transferases of human cornea. 390 21

Analogous to the liver, ocular tissues contain large concentrations of glutathione and are exposed to potentially damaging chemical compounds. Since glutathione has been shown to have a detoxification function, via mercapturic acid production in the liver, we investigated whether glutathione has a similar function in ocular tissues. We have demonstrated the presence of all of the enzymes involved in the mercapturic acid pathway i.e. glutathione S-transferase, gamma-glutamyl transpeptidase, cysteinylglycinase, and N-acetyl transferase, in the ocular tissues of bovine lens, cornea, retina, and retinal pigmented epithelium. Therefore glutathione may have another function in ocular tissues, that of the detoxification of xenobiotics.
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PMID:Mercapturic acid pathway enzymes in bovine ocular lens, cornea, retina and retinal pigmented epithelium. 612 91

Recently, a mouse glutathione S-transferase (GST) isozyme, mGSTA4-4, which belongs to a distinct group of GSTs has been characterized in our laboratory. During the present studies, Western blot analyses of bovine ocular tissues using the antibodies raised against the recombinant mGSTA4-4 obtained by expression in Escherichia coli revealed that the orthologs of mGSTA4-4 were present in cornea, retina, iris-ciliary body and sclera, but absent in lens. These novel GST isozymes of bovine ocular tissues were purified by immunoaffinity chromatography using the antibodies against rec-mGSTA4-4 and were designated as bGST 5.8 (their pI value being 5.8). Amino acid sequences of CNBr fragments of bGST 5.8 from cornea, sclera, retina and iris-ciliary body showed high degree of primary structure homologies with the corresponding regions of mGSTA4-4 indicating these bovine GST isozymes were distinct from the alpha. mu and pi group GSTs and were the newest members of the group of GSTs to which mGSTA4-4 belongs. There were significant differences among the amino acid sequences of bGST 5.8 of cornea and iris-ciliary body and retina suggesting presence of at least two closely related genes at bGST 5.8 locus. bGST 5.8 isozymes showed high activity toward 4-HNE (four-to-five-fold higher than that towards 1-chloro-2,4-dinitrobenzene), expressed GSH-peroxidase activity towards fatty acid hydroperoxides and phospholipid hydroperoxides, and showed GSH-conjugating activity towards fatty acid epoxides suggesting that these isozymes may play an important role in protection mechanism against the endogenous toxicants formed during lipid peroxidation.
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PMID:A group of novel glutathione S-transferase isozymes showing high activity towards 4-hydroxy-2-nonenal are present in bovine ocular tissues. 783 4

BP180 is a 180kDa hemidesmosomal protein recognized by bullous pemphigoid (BP) and pemphigoid gestationis (PG) autoantibodies. Recent cloning and sequence analysis performed by our laboratory have revealed that BP180 is a transmembrane protein with a long extracellular collagen-like region. A rabbit polyclonal antibody has been generated against a recombinant protein, designated GST-N delta 1, containing a segment of the BP180 ectodomain. The resulting antiserum, RN delta 1A, was shown to specifically react with BP180 on immunoblot, and labelled the extracellular region of the epidermal hemidesmosome on immunoelectron microscopy. A panel of normal and neoplastic human tissues were analysed by indirect immunofluorescence (IF) and RN delta 1A, to determine the distribution of BP180. A total of nine basal cell carcinomas (BCCs) and four squamous cell carcinomas (SCCs) of the skin were also studied. Intense IF staining was seen along the basement membrane zone (BMZ) of the epidermis, hair follicles, and the periphery of sebaceous gland lobules. The sebaceous lobules showed more intense staining in areas close to the duct. The epithelial BMZ of the following tissues also reacted with RN delta 1A: cornea, ocular conjunctiva, buccal mucosa, upper oesophagus, placenta (amnion placentum), umbilical cord and transitional epithelium of the bladder. The epithelium of the jejunum and ovary failed to react with RN delta 1A. Staining of the BCCs and SCCs was variable. Five of six nodular BCCs showed some anti-BP180 staining at the tumour-stromal interface, although the level of staining was less intense than that observed in the overlying normal epidermis. All three morphoeic BCCs analysed in this investigation did not show any staining with RN delta 1A. Three of four SCCs showed weak staining at the tumour-stromal interface. Thus, the tissue distribution of BP180 paralleled that of hemidesmosomes, and expression of this protein was found to be decreased or absent in cutaneous neoplasms.
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PMID:Expression pattern of the bullous pemphigoid-180 antigen in normal and neoplastic epithelia. 854 92


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