Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.2.3 (glutathione synthetase)
 678 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of enzyme systems are important in the protection of cells from chemical-induced oxidative damage. Little is known of the relative importance of these enzymes during postnatal development and its is possible that changes in their activity during this period may alter the susceptibility to toxic agents. This study investigated the activities of glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase, gamma-glutamyl-cysteine synthetase and glutathione synthetase in the liver, lung and kidney of postnatal and adult mice. The first 3 postnatal weeks are characterized by marked changes in the activities of enzymes that protect against oxidative stress (glutathione peroxidase/reductase, catalase and superoxide dismutase). Overall, the activity of these enzymes suggests that the mouse has a higher level of protection against peroxides at various stages during this period but lower capacity to detoxify superoxide anions. The activities of the glutathione-synthetic enzymes (gamma-glutamylcysteine synthetase and glutathione synthetase) were significantly lower in the kidney of the postnatal mice, but the liver and lung had levels similar to those in the adult. Glutathione turnover in the liver of 2-week-old mice was not different from that in adults. The results indicate a complex pattern of development in the activities of detoxification enzyme systems during postnatal development.
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PMID:Postnatal development of enzyme activities associated with protection against oxidative stress in the mouse. 196 50

The effect of protoporphyrin (PP) administration on the activities of enzymes related to and/or involved in lipid peroxidation and on the content of reduced glutathione (GSH) was investigated in rat liver. PP, at an intravenous dose of 20 mg/kg, increased GSH content, caused a weak suppression of NADPH-cytochrome c reductase activity and a slight increase of gamma-glutamyl transpeptidase activity 24 h after dosing, but had no effect on the activities of other enzymes such as xanthine oxidase, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, gamma-glutamylcysteine synthetase or glutathione synthetase. Treatment of rats with diethyl maleate following PP injection resulted in the disappearance of antioxidative action of PP. Furthermore, sinusoidal, but not canalicular, efflux of hepatic GSH was decreased by the PP treatment. The increase of liver GSH content by PP treatment due to the decrease of sinusoidal efflux of GSH from the liver, thus would be involved in the exertion of antioxidative action of PP.
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PMID:Antioxidative effect of protoporphyrin and increase of glutathione in protoporphyrin-administered rat liver. 810 76

The present study demonstrates the activities of antioxidant and glutathione-associated enzymes and the level of glutathione in Wilms' tumour (nephroblastoma) samples after chemotherapy (mainly actinomycin D and vincristine). We observed higher activity of superoxide dismutase in Wilms' tumour compared to adjacent morphologically unchanged kidney. On the other hand, in this tumour lower activities of catalase and the glutathione-associated enzymes glutathione synthetase, gamma-glutamyl transpeptidase, glutathione reductase and total glutathione S-transferases (GST) were found. Using isoelectric focusing we separated different forms of GST in tested tissues and revealed lower activities of the basic enzymes in Wilms' tumour, which may be responsible for the decrease of total GST activity. Moreover, we found the acidic isoenzymes to be the predominant class of GST in nephroblastoma. In Wilms' tumours with unfavourable histology a high activity of these isoenzymes together with a high level of GSH were observed. We suggest that these parameters may participate in the known phenomenon of anticancer drug resistance of tumours with unfavourable histology.
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PMID:Antioxidant and glutathione-associated enzymes in Wilms' tumour after chemotherapy. 869 48

Activities of enzymes that protect the retina from reactive oxygen species were investigated in experimentally diabetic rats and experimentally galactosemic rats, two animal models known to develop vascular lesions consistent with diabetic retinopathy. Diabetes or experimental galactosemia of 2 months duration significantly decreased the activities of glutathione reductase and glutathione peroxidase in the retina while having no effect on the glutathione synthesizing enzymes glutathione synthetase and gamma-glutamyl cysteine synthetase. Activities of two other important antioxidant defense enzymes-superoxide dismutase (SOD) and catalase-also were decreased (by more than 25%) in retinas of diabetic rats and galactosemic rats. Administration of supplemental antioxidants, vitamins C and E, for the 2 months prevented the diabetes-induced impairment of antioxidant defense system in the retina. In experimentally galactosemic rats, the supplemental antioxidants were not as effective: SOD activity was normalized, but the enzymes of the glutathione redox cycle were only partly restored, and the subnormal catalase activity was unaffected. Diabetes or experimental galactosemia results in significant impairment of the antioxidant defense system in the retina, and exogenous antioxidant supplementation can help alleviate the subnormal activities of antioxidant defense enzymes.
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PMID:Abnormalities of retinal metabolism in diabetes or experimental galactosemia. IV. Antioxidant defense system. 901 21

Previously we reported that expression of GSH1 (gamma-glutamylcysteine synthetase) and GSH2 (glutathione synthetase) of the yeast Saccharomyces cerevisiae was increased by heat-shock stress in a Yap1p-dependent fashion and consequently intracellular glutathione content was increased [Sugiyama, Izawa and Inoue (2000) J. Biol. Chem. 275, 15535-15540]. In the present study, we discuss the physiological role of glutathione in the heat-shock stress response in this yeast. Both gsh1 and gsh2 mutants could acquire thermotolerance by mild heat-shock stress and induction of Hsp104p in both mutants was normal; however, mutant cells died faster by heat shock than their parental wild-type strain. After pretreatment at a sublethal temperature, the number of respiration-deficient mutants increased in a gsh1 mutant strain in the early stages of exposure to a lethal temperature, although this increase was partially suppressed by the addition of glutathione. These results lead us to suspect that an increase of glutathione synthesis during heat-shock stress is to protect mitochondrial DNA from oxidative damage. To investigate the correlation between mitochondrial DNA damage and glutathione, mitochondrial Mn-superoxide dismutase (the SOD2 gene product) was disrupted. As a result, the rate of generation of respiration-deficient mutants of a sod2 delta strain was higher than that of the isogenic wild-type strain and treatment of the sod2 delta mutant with buthionine sulphoximine, an inhibitor of glutathione synthesis, inhibited cell growth. These results suggest that glutathione synthesis is induced by heat shock to protect the mitochondrial DNA from oxidative damage that may lead to cell death.
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PMID:Role of glutathione in heat-shock-induced cell death of Saccharomyces cerevisiae. 1106 59

Exposure of living organisms to reactive oxygen species (ROS), notably oxygen free radicals and hydrogen peroxide is closely linked to the very fact of aerobic life. Oxidants, however, are not always detrimental for cell survival, indeed moderate concentrations of ROS serve as signaling molecules. To maintain this level, cells have evolved an antioxidant defense system. Disruption of this balance leads either to oxidative or reductive stress. Down syndrome (DS) is a genetic disorder associated with oxidative stress. Overexpression of superoxide dismutase-1 (SOD-1) as a result of gene loading is suggested to be responsible for this phenomenon. To examine this view, we investigated the expression of thirteen different proteins involved in the cellular antioxidant defense system in brains of control and DS fetuses by two-dimensional electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization mass spectroscopy (MALDI-MS). No detectable change was found in expression of SOD-1, catalase, phospholipid hydroperoxide glutathione peroxidase, glutathione reductase, antioxidant enzyme AOE372, thioredoxin-like protein and selenium binding protein between control and DS fetuses. By contrast, a significant reduction was observed in levels of glutathione synthetase (P < 0.01), glutathione-S-transferase mu2 (P < 0.01), glutathione-S-transferase p (P < 0.05), antioxidant protein 2 (P < 0.05), thioredoxin peroxidase-I (P < 0.05) and thioredoxin peroxidase-II (P < 0.01) in DS compared with controls. The data suggest that oxidative stress in fetal DS does not result from overexpression of SOD-1 protein, rather oxidative stress appears to be the consequence of low levels of reducing agents and enzymes involved in removal of hydrogen peroxide.
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PMID:Antioxidant proteins in fetal brain: superoxide dismutase-1 (SOD-1) protein is not overexpressed in fetal Down syndrome. 1177 62

In certain tissues, glutathione biosynthesis is connected to methionine metabolism via the trans-sulfuration pathway. The latter condenses homocysteine and serine to cystathionine in a reaction catalyzed by cystathionine beta-synthase followed by cleavage of cystathionine to cysteine and alpha-ketoglutarate by gamma-cystathionase. Cysteine is the limiting amino acid in glutathione biosynthesis, and studies in our laboratory have shown that approximately 50% of the cysteine in glutathione is derived from homocysteine in human liver cells. In this study, we have examined the effect of pro- and antioxidants on the flux of homocysteine through the trans-sulfuration pathway in the human hepatoma cell line, HepG2. Our studies reveal that pyrrolidine dithiocarbamate and butylated hydroxyanisole enhance the flux of homocysteine through the trans-sulfuration pathway as has been observed previously with the pro-oxidants, H(2)O(2) and tertiary butyl hydroperoxide. In contrast, antioxidants such as catalase, superoxide dismutase and a water-soluble derivative of vitamin E elicit the opposite effect and result in diminished flux of homocysteine through the trans-sulfuration pathway. These studies provide the first evidence for the reciprocal sensitivity of the trans-sulfuration pathway to pro- and antioxidants, and demonstrate that the upstream half of the glutathione biosynthetic pathway (i.e. leading to cysteine biosynthesis) is redox sensitive as is the regulation of the well-studied enzymes in the downstream half (leading from cysteine to glutathione), namely, gamma-glutamyl-cysteine ligase and glutathione synthetase.
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PMID:Redox regulation of homocysteine-dependent glutathione synthesis. 1263 46

Little is known about the roles of androgens in the regulation of redox state in the prostate, a cellular process believed to profoundly influence normal and aberrant prostate functions. We demonstrate that castration induced discrete oxidative stress (OS) in the acinar epithelium of rat ventral prostate (VP), as evident from marked increases in 8-hydroxy-2'-deoxy-guanosine and 4-hydroxynonenal protein adducts in the regressing epithelium. Testosterone replacement partially reduced OS in VP epithelia of castrates, but the level remained higher than in intact rats. Quantification of steady-state mRNA levels of 14 genes involved in the anabolism and catabolism of reactive oxygen species (ROS) showed that castration resulted in dramatic increases of three ROS-generating NAD(P)H oxidases (Noxs) including Nox1, gp91(phox), and Nox4, significant reductions of key ROS-detoxifying enzymes (superoxide dismutase 2, glutathione peroxidase 1, thioredoxin, and peroxiredoxin 5), and unchanged levels of catalase, glutathione reductase, gamma-glutamyl transpeptidase, and glutathione synthetase. Testosterone replacement in castrated rats partially reduced expression of Noxs but restored expression of superoxide dismutase 2, glutathione peroxidase 1, thioredoxin, and peroxiredoxin 5 to complete normalcy and induced a compensatory increase in expression of catalase, glutathione reductase, gamma-glutamyl transpeptidase, and glutathione synthetase in the regenerating VP. Expression of superoxide dismutase 1, glutathione S-transferase-pi, and glucose-6-phosphate dehydrogenase was unaffected by castration and testosterone replacement. These findings indicate androgen-deprivation induces OS in the rat VP through elevation of ROS anabolism and diminution of antioxidant detoxification. Androgen replacement partially reduces OS in rat VP to precastration levels. Expression of Noxs remained high amid a broad-based recovery of antioxidant defense mechanism(s). These data might have implications on the use of androgen blockade for prostate cancer prevention and androgen therapy for andropause treatment in elderly men.
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PMID:Androgenic regulation of oxidative stress in the rat prostate: involvement of NAD(P)H oxidases and antioxidant defense machinery during prostatic involution and regrowth. 1463 23

Cellular defense system, including glutathione, glutathione-related enzymes, and antioxidant and redox enzymes, may play crucial roles in the aging of aerobic organisms. To understand the physiological roles of these factors in the aging process, their levels were compared in the livers and brains of 5-week- and 9-month-old rats. GST activity was higher in livers and brains of 9-month-old rats than in those of 5-week-old rats, and brain catalase activity was about 2-fold higher. However, it was unchanged in the livers of the 9-month-old rats. gamma-Glutamylcysteine synthetase activity was about 2-fold higher in the brains of the older rats but again not in their livers. In contrast glutathione synthetase activity appeared to be lower in the livers of the older rats while GSH content did not change with age in livers and brains. Glutathione peroxidase activity was higher in 9-month-old rat brains, but lower in 9-month-old rat livers, while superoxide dismutase activity was higher in both tissues in the older rats. The activities of two redox enzymes, thiol-transferase and thioredoxin reductase, did not change with age, nor did that of glutathione reductase. These results indicate that levels of different cellular defense systems vary with age in an irregular manner.
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PMID:Age-related changes in the activity of antioxidant and redox enzymes in rats. 1474 15

Alcoholic extract of the stems of Coscinium fenestratum, a medicinal plant indigenous to India and Sri Lanka used in ayurveda and siddha medicine for treating diabetes, was studied for its carbohydrate metabolism effect and antioxidant status in streptozotocin-nicotinamide induced type 2 diabetic rats. Oral administration of C. fenestratum stem extract in graded doses caused a significant increase in enzymatic antioxidants such as catalase, superoxide dismutase, glutathione synthetase, peroxidase, and glutathione peroxidase and in the nonenzymatic antioxidants ascorbic acid, ceruloplasmin and tocopherol. Effects of alcoholic extract on glycolytic enzymes such as glucose-6-phosphate dehydrogenase, lactate dehydrogenase and hexokinase showed a significant increase in their levels, whereas a significant decrease was observed in the levels of gluconeogenic enzyme, glucose-6-phosphatase and alanine aminotransferase in treated diabetic rats. Serum creatinine and urea levels also declined significantly. This investigation demonstrates significant antidiabetic activity of C. fenestratum.
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PMID:Alcoholic stem extract of Coscinium fenestratum regulates carbohydrate metabolism and improves antioxidant status in streptozotocin-nicotinamide induced diabetic rats. 1613 16


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