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)

This study examined whether brief repeated myocardial ischemia altered free radical generating and scavenging activity in a dog model. In dogs preconditioned with four 5-min left anterior descending coronary artery (LAD) occlusions and reperfusions, we examined transcardiac changes in both the function of neutrophils, cells which are major free radical generators, and in myocardial antioxidant enzyme activity, as an indication of free radical scavenging. Neutrophil function was assessed by determining luminol-enhanced whole blood chemiluminescence (CL) induced by zymosan. Blood was taken simultaneously from the carotid artery and the cardiac vein running along the occluded LAD. Preconditioning with sublethal ischemia significantly reduced whole blood CL in the cardiac vein compared with the carotid artery after the first and fourth 5-min reperfusions, while there was no difference in neutrophil count between these sampling sites. Immediately after brief repeated ischemia and reperfusion, manganese-superoxide dismutase (SOD) activity was significantly enhanced, and glutathione reductase activity was markedly reduced in the ischemic, compared with the non-ischemic, myocardium. There were no differences in the myocardial activities of copper, zinc-SOD, glutathione peroxidase, and glutathione S-transferase between the ischemic and non-ischemic regions. Also, no difference was observed between the reduced myocardial glutathione levels in these regions, although the oxidized glutathione level was significantly higher in the ischemic regions of the subepicardial and subendocardial areas. We demonstrated that brief repeated ischemia affects free radical generating and scavenging systems in the ischemic myocardium.
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PMID:Brief myocardial ischemia affects free radical generating and scavenging systems in dogs. 840 20

In 31 male patients undergoing coronary bypass surgery who underwent different periods of cardioplegic hypothermic arrest, the activities of glutathione peroxidase, glutathione reductase, glutathione transferase, copper/zinc-containing and manganese-containing superoxide dismutases, and catalase were studied in the right atrial myocardium, before and 5 minutes after aortic cross-clamping. The levels of thiobarbituric acid reactive substances (TBARS) and nonproteic thiol compounds (NP-SH) were also assessed. Prolonged ischemia followed by reperfusion induced activation of the major myocardial antioxidant enzymes with marked NP-SH depression and TBARS increase, despite cold crystalloid cardioplegic protection. These changes were significantly related to the duration of the ischemic arrest, suggesting: (1) that reperfusion free radical generation is dependent on the severity of the previous ischemic period; and (2) the occurrence of myocardial oxidative stress during cardiopulmonary bypass.
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PMID:Myocardial antioxidant defenses during cardiopulmonary bypass. 846

Immunolocalization studies of hamster kidney development were performed using polyclonal antibodies to antioxidant enzymes, including antibodies to copper, zinc and manganese superoxide dismutases, catalase, glutathione peroxidase and glutathione S-transferases and their subunits. Antibodies to extracellular matrix proteins were also studied to determine the temporal sequence between expression of immunoreactive protein for basement membrane proteins, which serve as markers of embryonic induction of nephron development, and antioxidant enzyme expression in kidney development. Immunoreactive proteins for antioxidant enzymes were not detectable in the developing kidney until after extracellular matrix proteins had been deposited. However, immunoreactive proteins for the antioxidant enzymes copper, zinc and manganese superoxide dismutases, catalase, and alpha class glutathione S-transferase Ya subunit were detected in renal tubules before birth. mu class glutathione S-transferase subunits Yb1 and Yb2 stained transitional epithelium at high levels before birth. Our results indicate: (1) each type of kidney cell has a unique antioxidant enzyme profile, (2) antioxidant enzymes are expressed in different types of cell at different times during development, but antioxidant enzyme immunoreactive protein was not present until after immunoreactive proteins for extracellular matrix molecules were detected, and (3) certain antioxidant enzymes are present before birth, indicating that high oxygen tension present at birth is not crucial for induction of immunoreactive protein.
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PMID:Immunohistochemical localization of antioxidant enzymes during hamster kidney development. 855 Mar 76

Immunogold studies of normal human kidney and common human kidney cancers were performed using polyclonal antibodies to antioxidant enzymes, including antibodies to copper, zinc and manganese superoxide dismutases, catalase, glutathione peroxidase, and glutathione S-transferases and their subunits. Normal tissue adjacent to human renal tumors had the same antioxidant enzyme immunoreactive protein profiles as normal human kidney, thus establishing that the presence of tumor does not alter the levels of antioxidant enzyme immunoreactive proteins in adjacent kidney tissue. Levels of immunoreactive protein for antioxidant enzymes were determined in four common types of malignant renal cancer. In general, tumors had low levels of antioxidant enzymes; however, certain histologic types of renal tumors had high levels of immunoreactive protein for glutathione S-transferase subunits, which could affect their susceptibility to chemotherapy. Studies of transitional carcinoma of the renal pelvis were especially informative since it was possible to compare levels of antioxidant enzyme immunoreactive protein with adjacent normal transitional epithelium; the majority of antibodies resulted in lower levels of immunoreactive protein in transitional cell carcinoma than in adjacent normal transitional epithelium. Our results are discussed in relation to the response of renal tumors to therapy.
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PMID:Immunogold analysis of antioxidant enzymes in common renal cancers. 872 Apr 59

Samples of normal human lung and six major types of human lung carcinomas were immunostained for antioxidant enzymes (manganese and copper, zinc superoxide dismutases, catalase, and glutathione peroxidase) and six isoenzymes of glutathione S-transferase staining was generally low in tumor cells compared with the high level of staining noted in respiratory epithelium. A notable exception was heterogeneity in immunostaining for manganese superoxide dismutase in lung adenocarcinoma, which showed both positive and negative cells in the same tumor. Tumor stromal cells (fibroblast-appearing cells) often showed strong immunostaining for manganese superoxide dismutase, while stromal cells were negative for other antioxidant and glutathione S-transferase enzymes. None of the carcinomas studied had significant levels of catalase or glutathione peroxidase; this finding has potential clinical relevance since it indicates that these tumors cannot detoxify hydrogen peroxide. The low levels of antioxidant and glutathione S-transferase enzymes in tumor cells is consistent with the hypothesis that these enzymes are markers of cell differentiation.
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PMID:An immunohistochemical analysis of antioxidant and glutathione S-transferase enzyme levels in normal and neoplastic human lung. 893 Jun 26

Glutathione transferase (GST) from octopus hepatopancreas was rapidly inactivated by micromolar concentration of Cu(II) in the presence of ascorbate at neutral pH and 0 degree C. Omitting the metal ion or ascorbate, or replacing the Cu(II) with Fe(II) did not result in any inactivation. Glutathione or the conjugation product of glutathione and 1-chloro-2,4-dinitrobenzene offered complete protection of the enzyme from Cu(II)-induced inactivation. 1-Chloro-2,4-dinitrobenzene, however, did not provide any protection. The inactivation was time and Cu(II) concentration dependent. The dependence of inactivation rate on Cu(II) concentration displayed saturation kinetics, which suggests that the inactivation occurs in two steps with Cu(II) binding with the enzyme first (KdCu = 260 microM), then the locally generated free radicals modify the essential amino acid residues in the active center, which results in enzyme inactivation. The Cu(II)-ascorbate system is, thus, an affinity reagent for the octopus GST. The enzyme inactivation was demonstrated to be followed by protein cleavage. Native octopus GST has a subunit M(r) of 24,000. The inactivated enzyme was cleaved at the C-terminal domain (domain II) of the enzyme molecule and resulted in the formation of peptide fragment of M(r) 15,300, which has the identical N-terminal amino acid sequence as the native enzyme. The other half of the peptide with M(r) approximately 7700 was visible in the gels only after silver staining, which also revealed a minor cleavage site, also located at the domain II, to produce peptide fragments of M(r) approximately 11,300 and 8300. The oxygen carrier molecule in the cephalopods' blood is the copper-containing hemocyanin, which during turnover will release Cu(II). Our results indicate that Cu(II) catalyzes a site-specific oxidation of the essential amino acid residues at the C-terminus of GST causing enzyme inactivation. The modified-enzyme is then affinity cleaved at the putative metal binding site. The ability of octopus GST to bind with free Cu(II) may have important biological implications to enable cephalopods to avoid copper-induced cellular toxicity.
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PMID:Metal-catalyzed oxidation and cleavage of octopus glutathione transferase by the Cu(II)-ascorbate system. 893 81

Exposure of animals to cadmium (Cd) (25 mg kg(-1) body wt day(-1)) for 10 weeks resulted in preferential accumulation of the metal in liver and kidney. Cd accumulation concomitantly increased zinc (Zn) concentration in both the organs. However, significant decrease in copper level was observed in liver, whereas kidney showed increase in copper (Cu) level. Cd exposure resulted in decreased total GST activity in liver (63%) and kidney (41%) as compared to control group monkeys on normal diet (group I). On isoelectric focusing (IEF) control liver GST segregated into thirteen isoenzymes, while in Cd-treated experimental animals (group II) liver GST resolved into nine isoenzymes. Similarly kidney GST from control animals separated into seven isoenzymes as compared to four isoenzymes from Cd-treated animals. Kinetic analysis showed that Cd exposure did not alter the affinity constant (Km) of GST for GSH and CDNB whereas maximal velocity (Vmax) for these substrates decreased as compared to controls in both the organs, indicating inhibition in GST synthesis by Cd. Cd resulted in a noncompetitive type of inhibition with respect to GSH in vitro. On isoelectric focussing GST of liver and kidney in group II resolved into nine and four isoenzymes as compared to thirteen and seven in group I, showing loss of four basic isoenzymes in case of liver and three isoenzymes in case of kidney. Monkey liver and kidney expressed all the three classes of GST isoenzymes i.e. alpha, mu and pi, which were serologically identical to human alpha, mu and pi GSTs.
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PMID:Alterations in isoforms of glutathione S-transferase in liver and kidney of cadmium exposed rhesus monkeys: purification and kinetic characterization. 904 21

To examine effects of exogenous Cd on the kidney antioxidant defense system (AOS) and the possible protective role of Se against Cd toxicity, male Wistar albino rats (2 months old) were exposed during 30 days to oral intake of 200 ppm Cd (as CdCl2), 0.l ppm Se (as Na-selenite) or to the same doses of Cd / Se, simultaneously. Marked accumulation of Cd (23.44 +/- 0.69 micrograms/g w.m.) and marked alterations of AOS, resulting in kidney injury (renal pseudohypertrophy), were found in Cd-treated rats. Activities of total superoxide dismutase (SOC, EC 1.15.1.1), manganese-containing superoxide dismutase (MnSOD) and selenium-dependent glutathione peroxidase (Se GSH-Px, EG 1.11.1.9) were significantly reduced, whereas that of glutathione-S-transferase (CST, EC 2.5.1.18) and vitamin E (vit E) concentration were significantly increased in the kidneys of Cd-treated rats. Kidney catalase (CAT, EC 1.11.1.6) activity, ascorbic acid (AsA) and red blood cell glutathione (GSH, GSSG) levels were not markedly influenced by CD uptake. In kidneys of Se treated rats, the activities of total SOD, copper-zinc-containing superoxide dismutase (CuZnSOD) and GST were significantly increased Activities of kidney CAT and Se GSH-Px were largely unchanged, whereas significant increases of the kidney AsA and vit E concentrations occurred. In Cd + Se-cotreated rats, the kidney activities of MnSOD, CAT and Se GSH-Px, as well as vit E concentration, were the same as in controls, whereas CuZnSOD and GST activities and concentration of AsA exceeded normal values. These data indicate that Se only partially improves the AOS that is insufficient to prevent Cd-induced nephrotoxicity.
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PMID:Effect of cadmium and selenium on the antioxidant defense system in rat kidneys. 921 17

We have isolated from bovine brain a protein with a high capacity to inhibit the copper ion-catalyzed oxidation of L-ascorbate and identified it as S100b protein, an EF-hand calcium-binding protein, by sequencing its proteolytic peptides. Copper binding studies showed that this protein has four copper-binding sites per dimeric protein molecule with a dissociation constant of 0.46 microM and that in the presence of L-ascorbate, copper ions bind to a total of six binding sites with a great increase in affinity. Furthermore, we examined whether S100b protein can prevent copper-induced cell damage. Bovine S100b protein was found to suppress dose-dependently the hemolysis of mouse erythrocytes induced by CuCl2. We transformed Escherichia coli cells with pGEX-5X-3 vector containing a cDNA for rat S100b protein, so that this protein could be expressed as a fusion protein with glutathione S-transferase. The transformed cells were demonstrated to be markedly resistant to a treatment with CuCl2 plus H2O2 as compared with the control cells expressing glutathione S-transferase alone. These results indicate that S100b protein does suppress oxidative cell damage by sequestering copper ions.
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PMID:Identification of S100b protein as copper-binding protein and its suppression of copper-induced cell damage. 928 1

A panel of HepG2-derived cell lines (CAT-Tox [L] assay, Xenometrix), harboring stress genes consisting of a sequence for chloramphenicol acetyltransferase (CAT) under the transcriptional regulation from mammalian promoters and response elements, was exposed for 18-24 hr to aqueous suspensions of urban dusts (SRM-1648, SRM-1649, EHC-93) or PM2.5 particles (particulate matter < 2.5 micron). Expression of CAT protein was measured by enzyme-linked immunosorbent assay. Induction of the CAT genes was verified with benzo[a]pyrene (CYP1A1, cytochrome P450 1A1 promoter; GSTYa, glutathione transferase subunit Ya promoter; XRE, xenobiotic response element), cadmium sulfate, and copper sulfate (HMTIIa, metallothionein IIa promoter; HSP70, heat shock protein 70 promoter). The urban dust suspensions were active on CYP1A1, GSTYa, and XRE cell lines. SRM-1648 and SRM-1649 were twice as potent as EHC-93 per unit mass in inducing the xenobiotic-dependent responses, which correlated with contents in polycyclic aromatic hydrocarbons. These three reference particles, as well as six PM2.5 preparations collected on hi-vol filters in the Great Lakes basin, were also found to induce HMTIIa and HSP70, the magnitude of the responses correlating closely with the amount of soluble copper in the particulate preparations. The results indicate that bioavailable chemical species in the unfractionated particles can directly and quantitatively induce xenobiotic, metal, and stress-dependent responses in a target cell model, resulting in patterns of gene induction consistent with the chemical compositions of the environmental materials. We propose that cell culture models could be helpful for toxicodynamic inferences in adjunct to environmental monitoring and exposure assessments.
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PMID:Regulation of promoter-CAT stress genes in HepG2 cells by suspensions of particles from ambient air. 932 24


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