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)

Environmental pollutants that disrupt endocrine system might also affect the modeling and remodeling of bone. Environmental factors, irrespective of age and sex contribute for the development of secondary osteoporosis. Polychlorinated biphenyls have adverse effects on various organs including bone. The present study was designed to investigate the effects of PCB (Aroclor 1254) on femur bone and the ameliorative role of vitamin C or E. In this regard, four groups of adult male albino rats were used as control, PCB (2mg/kgb.wt.), PCB+vitamin C (100mg/kgb.wt.) and PCB+vitamin E (50mg/kgb.wt.). The bone formation markers (ALP, Collagen), bone resorption marker (TRAP), antioxidant enzymes (SOD, GPX and GST) and lipid peroxidation in the femur were studied. Aroclor 1254 treatment decreased the ALP activity and collagen, but increased the TRAP activity and lipid peroxidation. While it decreased the SOD and GPX activity, GST was unaltered. Interestingly, simultaneous administration of vitamin C or E prevented the adverse effects of Aroclor 1254 in the femur. In conclusion, the present investigation suggests that Aroclor 1254 induced oxidative stress affects femoral bone metabolism. However, vitamin C or vitamin E protected the femur from the oxidative stress.
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PMID:Effects of Aroclor 1254 on femoral bone metabolism in adult male Wistar rats. 1788 81

Cleaved high molecular weight kininogen (HKa), as well as its domain 5 (D5), inhibits migration and proliferation induced by angiogenic factors and induces apoptosis in vitro. To study its effect on tube formation we utilized a collagen-fibrinogen, three-dimensional gel, an in vitro model of angiogenesis. HKa, GST-D5 and D5 had a similar inhibitory effect of tube length by 90+/-4.5%, 86+/-5.5% and 77+/-12.9%, respectively. D5-derived synthetic peptides: G440-H455 H475-H485 and G486-K502 inhibited tube length by 51+/-3.7%, 54+/-3.8% and 77+/-1.7%, respectively. By a comparison of its inhibitory potency and its sequences, a functional sequence of HKa was defined to G486-G496. PP2, a Src family kinase inhibitor, prevented tube formation in a dose-dependent manner (100-400 nM), but PP3 at 5 microM, an inactive analogue of PP2, did not. HKa and D5 inhibited Src 416 phosphorylation by 62+/-12.3% and 83+/-6.1%, respectively. The C-terminal Src kinase (Csk) inhibits Src kinase activity. Using a siRNA to Csk, expression of Csk was down-regulated by 86+/-7.0%, which significantly increased tube length by 27+/-5.8%. The addition of HKa and D5 completely blocked this effect. We further showed that HKa inhibited Src family kinase activity by disrupting the complex of uPAR, alphavbeta3 integrin and Src. Our results indicate that the anti-angiogenic effect of HKa and D5 is mediated at least in part through Src family kinases and identify a potential novel target for therapeutic inhibition of neovascularization in cancer and inflammatory arthritis.
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PMID:The inhibition of tube formation in a collagen-fibrinogen, three-dimensional gel by cleaved kininogen (HKa) and HK domain 5 (D5) is dependent on Src family kinases. 1806 65

Hypertrophic scars and keloid are dermal proliferative disorders in wound healing. Transforming growth factor beta (TGF-beta) has been implicated in scar formation through the activation of fibroblasts and the acceleration of collagen deposition. Our study aimed to design a novel truncated (27-123 residues) type II TGF-beta receptor (tTGFbetaRII) and to determine its effects on the proliferation of keloid fibroblasts and the collagen synthesis as well as TGF-beta I expression of the cells. The coding sequences of TGF-beta I and tTGFbetaRII were amplified using RT-PCR and then cloned into pGBKT7 and pGADT7 vectors. A yeast two-hybrid experiment and a glutathione S-transferase (GST)-pull down assay were performed to verify the affinity of tTGFbetaRII to TGF-beta I. Our results indicated that treatment with tTGFbetaRII inhibited the growth of keloid fibroblasts and suppressed the synthesis of type I collagen in keloid fibroblasts in a concentration-dependent manner. Moreover, northern and western blot analysis revealed a decline of the TGF-beta I expression at both mRNA and protein levels after exposure to 5, 10 or 20 mug/ml of tTGFbetaRII. Together, our data suggested that the exogenous tTGFbetaRII can efficiently trap TGF-beta I from access to wild-type receptors and can suppress TGF-beta I triggered signals. Thus it may potentially be clinically applied to scar therapy.
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PMID:A novel truncated TGF-beta receptor II downregulates collagen synthesis and TGF-beta I secretion of keloid fibroblasts. 1838 95

Organotypic cultures of human breast skin incubated with silver bandage or treated with silver sulfadiazine accumulated silver in epithelial cells and in macrophages, fibroblasts and collagen fibrils and fibres of underlying connective tissue. Ultrastructurally, the accumulated silver was found in lysosome-like vesicles of the different cells and evenly spread along collagen structures. Apoptotic nuclei were present but few. Autometallographic amplification of 2D-PAGE gels revealed that glutathione S-transferase and glutathion detoxify silver ions in the epidermal cell by binding them in silver-sulphur nanocrystals. Thus, the cytotoxic effect of silver ions seems to be muted by silver ions by being: (1) taken up by undamaged cells, neutralised by glutathione (GSH) and accumulated in lysosomal vesicles, (2) bound extracellularly to SH-groups of the collagen fibres.
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PMID:Ultrastructural localization and chemical binding of silver ions in human organotypic skin cultures. 1839 36

The effect of Picroliv on hepatic microsomal mixed-function oxidases (MFO) and glutathione conjugating enzyme system in cholestatic rats was studied. Bile duct ligation in male rats for one weeks caused significant increase in both serum sorbitol dehydrogenase activity and serum bile acide concentration indicating cholestatic liver injury. Furthermore, a rise in the hepatic hydroxyproline level indicating collagen accumulation was observed. As a result of these alterations, the hepatic microsomal MFO system was imparied as evidenced by a decrease in cytochrome P-450 system content and in the activities of NADPH-cytochrome C reductase and aminopyrine demethylase. While the hepatic glutathione content remained unaffected, the cytosolic glutathione S-transferase activity was clearly suppressed due to subchronic cholestasis. Oral administration of Picroliv (25 mg/kg/day for 21 days)--a standardized irioid glycoside fraction of Picrorhiza kurroa in bile ligation induced cholestatic rats, singnificantly prevented the biochemical changes induced in liver and serum of cholestatic rats. These results suggested that picroliv has anti-cholestatic activity which may be attributed to antioxidant property or it's specific role in protein synthesis.
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PMID:Effect of picroliv administration on hepatic microsomal mixed function oxidases and glutathione-conjugating enzyme system in cholestatic rats. 1869 26

Lysyl oxidase (LOX), an amine oxidase critical for the initiation of collagen and elastin cross-linking, has recently been shown to regulate cellular activities possibly by modulating the functions of growth factors. In this study, we investigated the interaction between LOX and transforming growth factor-beta1 (TGF-beta1), a potent growth factor abundant in bone, the effect of LOX on TGF-beta1 signaling, and its potential mechanism. The specific binding between mature LOX and mature TGF-beta1 was demonstrated by immunoprecipitation and glutathione S-transferase pulldown assay in vitro. Both proteins were colocalized in the extracellular matrix in an osteoblastic cell culture system, and the binding complex was identified in the mineral-associated fraction of bone matrix. Furthermore, LOX suppressed TGF-beta1-induced Smad3 phosphorylation likely through its amine oxidase activity. The data indicate that LOX binds to mature TGF-beta1 and enzymatically regulates its signaling in bone and thus may play an important role in bone maintenance and remodeling.
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PMID:Lysyl oxidase binds transforming growth factor-beta and regulates its signaling via amine oxidase activity. 1883 15

This study aimed to identify new diabetic nephropathy (DN)-related proteins and renal targets of the copper(II)-selective chelator, triethylenetetramine (TETA) in streptozotocin-diabetic rats. We used the recently developed iTRAQ technology to compare renal protein profiles among non-diabetic, diabetic, and TETA-treated diabetic rats. In diabetic kidneys, tubulointerstitial nephritis antigen (TINag), voltage-dependent anion-selective channel (VDAC) 1, and VDAC2 were up-regulated in parallel with alterations in expression of proteins with functions in oxidative stress and oxidative phosphorylation (OxPhos) pathways. By contrast, mitochondrial HSP 60, Cu/Zn-superoxide dismutase, glutathione S-transferase alpha3 and aquaporin-1 were down-regulated in diabetic kidneys. Following TETA treatment, levels of D-amino acid oxidase-1, epoxide hydrolase-1, aquaporin-1, and a number of mitochondrial proteins were normalized, with concomitant amelioration of albuminuria. Changes in levels of TINag, collagen VIalpha1, actinin 4alpha, apoptosis-inducing factor 1, cytochrome C, histone H3, VDAC1, and aquaporin-1 were confirmed by Western blotting or immunohistochemistry. Changes in expression of proteins related to tubulointerstitial function, podocyte structure, and mitochondrial apoptosis are implicated in the mechanism of DN and their reversal by TETA. These findings are consistent with the hypothesis that this new experimental therapy may be useful for treatment of DN.
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PMID:Quantitative proteomic profiling identifies new renal targets of copper(II)-selective chelation in the reversal of diabetic nephropathy in rats. 1963 43

This study aimed to investigate the possible protective role of curcumin against renal damage caused by administration of cyclosporine A (CsA) in adult male rats. For this purpose, 27 adult male albino rats were used and divided into three equal groups. Group I (control group) and group II (CsA-treated group) received a daily subcutaneous injection of CsA at a dose of 20 mg/kg b.w. Group III (prophylactic group) received a daily oral curcumin at a dose of 15 mg/kg b.w. simultaneously with CsA. After 21 days, all the animals were anaesthetized and the kidneys were rapidly removed and processed to prepare paraffin sections stained with H&E, PAS and Masson's trichrome. In addition, the glutathione S-transferase (GST) enzyme was detected immunohistochemically. The optical density and the area (in %) of positive GST immunoreactions were measured in the cytoplasm of renal tubules and glomeruli and the data were statistically analyzed. Examination of sections from CsA-treated group showed renal tubules with vacuolated cytoplasm and others with darkly stained pyknotic nuclei. Apical brush borders of proximal tubules were undefined and PAS positive granules were noticed in their cytoplasm. The renal corpuscles contained shrunken glomeruli with widening of their Bowman's spaces. Inflammatory cellular infiltrate and increase in the collagen fibers were observed between the renal tubules. In prophylactic group, the structure of renal tubules and corpuscles were preserved except few tubular darkly stained pyknotic nuclei. Numerous blood vessels, few cellular infiltration and thin collagen fibers were observed between the renal tubules. Statistical analysis of morphometric data showed significant increase in the optical density of GST immunoreactivity in the cells of renal tubules and glomeruli of CsA-treated group when compared with the control or prophylactic groups. However, a significant decrease in the area of GST immunoreactivity in sections from prophylactic group was observed when compared with control or CsA-treated groups. In conclusion, protective effect of curcumin against cyclosporine-induced nephrotoxicity in rats was proven based on the study of histological changes and GST immunoexpression. This study supposes the possible therapeutic applications of curcumin in CsA-treated patients.
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PMID:Prophylactic role of curcumin against cyclosporine-induced nephrotoxicity: histological and immunohistological study. 2037 85

Ethacrynic acid (Ea) is a substrate for glutathione transferase 7-7 (GST-P) in rat. Toxic effects of Ea have been related to its metabolism and GSH depletion, but resistance conferred by GSTP1-1 (the human homologue) has also been reported. Hepatocytes from enzyme altered foci (EAF) express GST-P, and a model for selection of resistant EAF cells has been developed using Ea as a toxic agent. In the present study the effects of Ea in this model have been characterized. Hepatocytes from foci-bearing rats were isolated. Isolated cells were exposed to Ea for 1-4 hr in suspension. They were then allowed to attach to collagen-coated plates in a serum-containing medium. Preferentially GST-P-positive cells attached after Ea treatment, thus increasing the number of positive cells per attached cells (GST-P-%). Extracellular GSH, as well as alpha-tocopherol, did not influence the Ea effect. However, the effect of Ea was counteracted by inhibitors of glutathione transferase activity. Taxol, a microtubule stabilizing agent, also counteracted the effect of Ea on GST-P-%. 1,2-Dichloro-4-nitrobenzene (DCNB, 0.4 mM), which is a substrate for other glutathione transferase isoenzymes than GST-P, also increased the GST-P-%. However, the effect of DCNB was not inhibited by taxol. It was also found that Ea induced a drop in ATP levels, but this effect, as well as cell leakage, came later than the loss of attachment. The data suggest that the critical effect of Ea was cytoskeletal changes, and that GST-P conferred resistance by detoxification of Ea.
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PMID:Resistance against ethacrynic acid in glutathione transferase 7-7 (GST-P)-positive hepatocytes isolated from carcinogen-treated rats: the role of cytoskeletal changes and ATP depletion. 2065 Jan 71

In order to investigate whether collagen gel sandwich and immobilization cultures of rat hepatocytes are suitable in vitro models for long-term pharmaco-toxicological studies, the expression of the key phase II biotransformation enzyme, glutathione S-transferase (GST, EC 2.5.1.18), has been studied in the presence or absence of l-proline (60mug/ml) in the culture medium. Additionally, hepatocytes morphology was followed and albumin secretion into the medium measured. As judged by inverse phase light microscopy and transmission electron microscopy, cells cultured in both organotypical models remained viable and well differentiated for at least 14 days. Albumin secretion increased 2.5-fold after 7 days of culture, in comparison with the values found after 2 days, and remained thereafter relatively constant. When l-proline was added to the medium of sandwich and immobilization gel cultures, steady-state secretion levels of 7.1 and 5.1 mug albumin/hr, respectively, were already obtained after 4 days of culture. Total, Mu, Alpha and Pi class GST activities were determined using a general substrate and isoenzyme specific substrates, respectively. After 7 days of culture, total GST activities were decreased as compared with the values obtained for freshly isolated cells. On the contrary, Mu class GST activities were kept at a constant level. Alpha class GSTs were maintained at a 50% activity level and GST 7-7 activity was shown to be slightly induced. l-proline prevented an initial decline in total and Mu class GST activities in both culture models. The GST subunit pattern, measured after affinity chromatography by reversed phase HPLC, reflected the GST activity results.
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PMID:Cell morphology, albumin secretion and glutathione S-Transferase expression in collagen gel sandwich and immobilization cultures of rat hepatocytes. 2065 29


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