Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A mouse glutathione S-transferase (GST) isozyme designated as GST 5.7 or mGSTA4-4 belongs to a distinct subclass of the alpha-class isozymes of GST. It is characterized by kinetic properties intermediate between the alpha- and pi-classes of GSTs. We have recently cloned and expressed this isozyme (rec-mGSTA4-4) in E. coli and have reported its complete primary sequence (Zimniak, P., et al. (1992) FEBS Lett., 313, 173-176). Using antibodies raised against the homogenous rec-mGSTA4-4 expressed in E. coli, we now demonstrate that an ortholog of this isozyme was selectively expressed in various human tissues. The human ortholog of mGST A4-4 purified from liver had a pI value of 5.8 and constituted approx. 1.7% of total GST protein of human liver. Similar to other alpha-class GSTs, the N-terminus of this isozyme (GST 5.8) was also blocked. CNBr digestion of the enzyme yielded two major fragments with M(r) values of 12 kDa and 6 kDa. The sequences of these two fragments showed identities in 16 out of 20 residues and 17 out of 20 residues with the corresponding sequences of its mouse ortholog (mGSTA4-4), and showed significant homologies with the rat and chicken orthologs, GST 8-8 and GST CL3. Human liver GST 5.8 showed more than an order of magnitude higher activity towards t-4-hydroxy-2-nonenal as compared to 1-chloro-2,4-dinitrobenzene. This isozyme also expressed glutathione-peroxidase activity towards fatty acid, as well as phospholipid hydroperoxides suggesting its role in protection mechanisms against the toxicants generated during lipid peroxidation. Western blot analysis of human tissues revealed that this GST isozyme was selectively expressed in human liver, pancreas, heart, brain and bladder tissues, but absent in lung, skeletal muscle, spleen and colon.
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PMID:A novel glutathione S-transferase isozyme similar to GST 8-8 of rat and mGSTA4-4 (GST 5.7) of mouse is selectively expressed in human tissues. 814 70

The glutathione transferases (GSTs) are a family of ubiquitous enzymes that catalyze the conjugation of reduced glutathione (GSH) with reactive electrophiles. Rat vascular tissue contains GST isoforms that represent a major cellular defense mechanism against atherogenic alpha,beta-unsaturated aldehydes (Misra et al., Toxicol. Appl. Pharmacol. 133, 27-33, 1995). In this study we examined the role of GSTs in providing protection to cultured neonatal vascular smooth muscle cells (VSMCs) from the alpha,beta-unsaturated carbonyl cardiovascular toxins, allylamine and its metabolite, acrolein. Confluent cultured cells were exposed to 2 to 10 microM allylamine (a cardiovascular toxin that is metabolized in vivo and in vitro by VSMCs to the reactive aldehyde, acrolein) or to acrolein (2-10 microM) for 48 h; dose-cytotoxicity curves were generated utilizing a tetrazolium-dependent cytotoxicity assay. Concommittant treatment with sulfasalazine, an established inhibitor of GST, was found to markedly increase allylamine- or acrolein-induced cytotoxicity, decreasing the LC50 by two- to threefold at 50 to 100 microM sulfasalazine. A clonogenic survival assay in VSMCs exposed to these compounds for 4 h confirmed lethal toxicity and enhanced toxicity following cotreatment with sulfasalazine. Isobologram analysis (which statistically defines the limits of additivity of two independent treatments) showed that the sulfasalazine effect on both allylamine and acrolein cytotoxicity was supraadditive, or synergistic. Sulfasalazine was not cytotoxic to VSMCs in the range of concentrations that augmented acrolein or allylamine cytoxicity; total GST activity was inhibited, however, in a dose-dependent manner in that range. GST purified by GSH-affinity chromatography from pelleted untreated cells gave specific activities and kinetic constants consistent with those previously reported for rat aorta total GSTs. The catalytic efficiency (Kcat/Vm) was found to be much greater for 4-hydroxy-2-nonenal than for 1-chloro-2,4-dinitrobenzene (0.058 vs 0.4 s-1 mM-1). Western blot of purified total GSTs using antibodies against rec-mGSTA4-4 revealed a single band at 25 kDa, confirming the presence of a GST isozyme immunologically similar to rat GST8-8, which is known to utilize alpha,beta-unsaturated carbonyls as preferred substrates. Our data indicate that GSTs are an important defense in the vascular media, protecting blood vessels against alpha,beta-unsaturated carbonyl cardiovascular toxins that are involved in initiating atherosclerotic lesions.
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PMID:The role of glutathione S-transferases as a defense against reactive electrophiles in the blood vessel wall. 977 3