Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ageing of WI-38 fibroblasts in culture was used as a model in order to investigate the evolution and the alteration of the key antioxidant enzyme glutathione peroxidase. The activity of glutathione peroxidase is influenced by the presence of selenium in the culture medium and we have also shown that the specific activity of this enzyme does not decrease during ageing, but rather slightly increases. No alteration could be detected by immunotitration. Also the kinetic parameter Km for tert-butyl hydroperoxide has not changed. However, the heat resistance of the enzyme dramatically decreases with ageing. Dilutions of the enzyme preparations had the same influence on the thermosensitivity of the enzyme. This dilution effect is most probably linked to the dissociation of the enzyme subunits into dimers and monomers. Moreover, the kinetic of thermoinactivation curves are best explained by consecutive reactions of inactivation with an intermediary enzyme form. These observations strongly support the hypothesis that ageing is associated with an increased dissociation constant of the tetrameric glutathione peroxidase leading to an easier dissociation of the enzyme in old cells.
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PMID:Alteration of enzymes in ageing human fibroblasts in culture. V. Mechanisms of glutathione peroxidase modification. 171 10

Selenosubtilisin, a semisynthetic enzyme produced by chemical modification of subtilisin's catalytic serine, mimics the antioxidant enzyme glutathione peroxidase, catalyzing the reduction of hydroperoxides by 3-carboxy-4-nitrobenzenethiol. In analogy with the natural peroxidase, a variety of hydroperoxides are accepted as substrates for the semisynthetic enzyme, whereas the dialkyl compound tert-butyl peroxide is not. Kinetic investigations reveal that kmax is dependent upon the nature of the hydroperoxide, indicating that peroxide-mediated oxidation of the enzymic selenolate is at least partially rate-limiting. Experiments with the radical trap 2,6-di-tert-butyl-4-methylphenol suggest that, while the nonenzymic reaction between tert-butyl hydroperoxide and thiol involves free radicals, the same reaction catalyzed by selenosubtilisin does not. The studies described here support the enzyme's proposed ping-pong mechanism and are consistent with previous mechanistic observations.
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PMID:Peroxide dependence of the semisynthetic enzyme selenosubtilisin. 826 74

There is increasing evidence that free radical scavengers play an important role in the aging process and the control of cellular growth. We purified a free radical scavenging protein, the water-soluble protein (WSP) from broad beans (Vicia faba). In this study, we examined the effect of WSP on cellular growth and in vitro life span in old human fetal lung fibroblasts (WI-38 and PDL 37-40, 78-84% of the maximum life span). Since WSP increased the cellular growth, we also examined the effect of WSP (1.25-5 microg/ml) on cytosolic antioxidant enzyme activities in the old cells treated or not with tert-butyl hydroperoxide (BHP) to elucidate the mechanisms of cell proliferation in the old cells. The cellular growth of old fibroblasts was greatly increased by WSP. In 1.25 and 2.5 microg/ml of WSP, the cell proliferation increased by 32 and 35%, respectively, as compared with controls. The maximum population doubling levels of the cells did not increase. In the cells incubated with BHP, the cytosolic superoxide dismutase activity was returned to its control value by WSP treatment (1.25-5 microg/ml). The cytosolic glutathione peroxidase activity progressively increased with increasing concentrations of WSP. On the other hand, the cytosolic superoxide dismutase activity after 1.25- and 2.5- microg/ml WSP treatment without BHP was increased by 189 and 144%, respectively. Similarly, the cytosolic glutathione peroxidase activity was increased by 67 and 53%, respectively. These results suggest that cytosolic antioxidant activities in old cells can be modulated by WSP treatment. We concluded that there was a correlation between the optimum WSP concentrations for the increase of cellular growth and the WSP concentrations required to exhibit these maximum enzyme activities.
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PMID:Increase of the cellular growth of old human diploid fibroblasts by radical scavenger: water-soluble protein from broad beans. 993 28

Recent findings in our laboratory showed that in citrus cells, salt treatment induced the accumulation of mRNA and a protein corresponding to phospholipid hydroperoxide glutathione peroxidase (PHGPX), an enzyme active in the cellular antioxidant system. The protein and its encoding gene, csa, were isolated and characterized, and the expected enzymatic activity was demonstrated (G. Ben-Hayyim et al., 1993, Plant Sci. 88: 129-140; D. Holland et al., 1993, Plant Mol. Biol. 21: 923-927; D. Holland et al., 1994, FEBS Lett. 337: 52-55; T. Beeor-Tzahar et al., 1995, FEBS Lett. 366: 151-155). In an attempt to find out how salt induces the expression of an antioxidant enzyme, the regulation of PHGPX in citrus cells was studied at both the mRNA transcript and the protein levels. A high and transient response at the csa mRNA level was observed after 4-7 h of exposing salt-sensitive cells to NaCl, or abscisic acid, whereas no response could be detected in the salt-tolerant cells under the same conditions. tert-Butylhydroperoxide, a substrate of PHGPX, induced csa mRNA transcripts after only 2 h, and abolished the differential response between salt-sensitive and salt-tolerant cells. On the basis of these results and those obtained under heat and cold stresses, it is suggested that csa is directly induced by the substrate of its encoded enzyme PHGPX, and that salt induction occurs mainly via the production of reactive oxygen species and hydroperoxides.
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PMID:Regulation of stress-induced phospholipid hydroperoxide glutathione peroxidase expression in citrus 1055 Jun 28

A diselenide, 2,2'-diseleno-bis-beta-cyclodextrin (2-SeCD), was synthesized to imitate the antioxidant enzyme glutathione peroxidase (GPX). The GPX mimic accepts a variety of hydroperoxides as substrates. The GPX activities, reduction of H(2)O(2), tert-butyl hydroperoxide and cumenyl hydroperoxide by glutathione, are 7.4, 4.5 and 10.2 U/micromol, respectively. In contrast to ebselen (PZ51), the diselenide displays high GPX-like activity. The reduction of hydroperoxide by glutathione in the presence of a radical trap shows that the mimic catalyzes the reaction via a non-radical mechanism. A ping-pong mechanism was observed in the steady-state kinetic studies of the 2-SeCD-catalyzed reaction.
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PMID:A bis-cyclodextrin diselenide with glutathione peroxidase-like activity. 1101 12

The modulation of garlic oil (GO) and three allyl compounds, diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS), on the antioxidation system in rat livers and red blood cells was examined. Rats were orally administered GO (200 mg/kg body weight), DAS (20, 80 mg/kg body weight), DADS (80 mg/kg body weight) or DATS (70 mg/kg body weight) three times a week for 6 weeks. Control rats received corn oil (2 ml/kg body weight) alone. GO, DADS and DATS treatment significantly increased the glutathione (GSH) content (48-84%) in red blood cells (P < 0.05). DATS displayed a greater enhancement than GO and DADS (P < 0.05). Hemolysis induced by tert-butyl hydroperoxide was not suppressed by GO or allyl compound treatment although higher GSH content was evident. Hepatic GSH was not influenced by garlic components. In rat livers, DADS and DATS significantly increased the activity of GSH reductase (46 and 54%, respectively) and of GSH S-transferase (GST) (63 and 103%, respectively), but decreased the GSH peroxidase activity (27 and 28%, respectively). In contrast, GSH reductase and GST activities in the DAS group, either 20 or 80 mg/kg body weight, were similar to the control group. A decrease of GSH peroxidase activity was observed in rats dosed with 80 mg/kg body weight (P < 0.05). An increase in GST activity and a decrease in GSH peroxidase activities were also noted in GO-treated rats (P < 0.05). In red blood cells, three GSH-related antioxidant enzyme activities were not affected by garlic oil and its organosulfur components. Immunoblot assay showed that, accompanying the increase in hepatic GST activity, GO, DADS, DAS (80 mg/kg body weight) and DATS increased the expression of GST Ya, Yb1 and Yc proteins. Results indicate that GO and three allyl compounds play a differential role in modulation of the GSH-related antioxidant system in rat livers and red blood cells.
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PMID:Effects of organosulfur compounds from garlic oil on the antioxidation system in rat liver and red blood cells. 1134 86

Previously, we found that macrophage colony-stimulating factor (M-CSF) could reduce tert-butyl hydroperoxide (tbOOH)-induced oxidative injury in monocytes/macrophages. In order to find the mechanism by which M-CSF achieves this, we investigate the effect of M-CSF on the antioxidant system in murine macrophage RAW264.7 cells, using L929 cell-conditioned medium (L929-CM) as the source of M-CSF. The results show that L929-CM increased selenium-dependent glutathione peroxidase, non-selenium-dependent glutathione peroxidase, and catalase activities; and it increased reduced glutathione (GSH) but decreased lipoperoxide content in RAW264.7 cells. L929-CM-treated cells maintained their antioxidant capacity (including antioxidant enzyme activities and GSH content) when challenged with tbOOH. We conclude that M-CSF from L929-CM reduces oxidative injury in RAW264.7 cells by increasing antioxidant enzyme activity and improving redox status.
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PMID:Effect of L929 cell-conditioned medium on antioxidant capacity in RAW264.7 cells. 1178 96

tert-Butyl hydroperoxide (t-BOOH), a membrane permeant oxidant, elicits enhanced vasoconstriction of perfused kidney and mesenteric arterial beds isolated from DOCA-salt-induced hypertensive rats. We hypothesize that enhanced vasoconstriction to t-BOOH during DOCA-salt hypertension involves free radical species and decreases in the expression of the endogenous antioxidant enzyme, superoxide dismutase (SOD). t-BOOH (0.01-50 micromol) dose-dependently constricted the perfused kidney and mesenteric vascular beds (MVB) of rats. Infusion of tempol (100 microM), a free radical scavenger, reduced the constrictor responses from 116.70+/-16.65% to 57.45+/-9.25% (kidneys) and from 72.91+/-3.70% to 48.10+/-0.10% (mesenteric beds). t-BOOH-induced vasoconstriction of both vascular beds were also significantly reduced in DOCA-salt rats treated chronically (15 mg/kg ip, 3 weeks) with tempol (DOCA/TEMPOL). Catalase (500 IU) did not attenuate t-BOOH-induced responses in vascular beds of DOCA/TEMPOL rats. Western blot analyses showed significant reduction in Cu/Zn-SOD expression in DOCA-salt versus sham rats of both vascular preparations; SOD expressions were protected from down-regulation in DOCA/TEMPOL vascular beds. This study suggests that free radical species is involved in both t-BOOH-induced constrictions and in the down-regulation of SOD protein expressions during DOCA-salt hypertension.
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PMID:Tert-butyl hydroperoxide-mediated vascular responses in DOCA-salt hypertensive rats. 1264 10

The influence of black currant juice, Bowman-Birk protease inhibitor (BBI), kolaviron (a biflavonoid fraction of Garcinia kola seed), sugars, vitamin C and tert-butyl hydroperoxide on a wide range of biomarkers for oxidative stress, DNA damage and sugar or lipid metabolism has been investigated in male F 344 rats. The selected pro-oxidant control, tert-butyl hydroperoxide, significantly increased plasma and liver 2-amino-adipic semialdehyde (AAS), a marker of protein oxidation (p <0.05) whereas lipid oxidation assessed as malon dialdehyde (MDA) and DNA oxidation were not significantly increased. Feeding BBI also increased the level of oxidized protein in plasma and liver at the higher dose level (0.5%). No effect was observed at the lower dose level (0.25%), which even decreased lipid oxidation in plasma. BBI did not affect background levels of DNA strand breaks or oxidation (comets). In rats exposed to black currant juice, a statistically significant decrease in liver AAS and MDA was observed. This effect could not be explained by its content of sugars or of the known redox active constituent, vitamin C. The lowering effect of black currant juice on protein and lipid oxidation was similar in magnitude to that of the known liver protectant, kolaviron. In rats treated with kolaviron (200 mg/kg body weight), background AAS levels were significantly reduced in both plasma and liver whereas the effect on MDA only reached statistical significance in plasma. Kolaviron was the only extract tested which decreased oxidative damage to DNA in the liver. The erythrocyte antioxidant enzyme activities, catalase and glutathione peroxidase were decreased in rats treated with tert-butyl hydroperoxide (p <0.05) but were not affected by the other treatments. Black currant juice and sugars increased plasma triglyceride levels and black currant juice increased plasma cholesterol but neither of them nor any other treatment affected blood glucose, erythrocyte HbA1c or fructosamine. We conclude that markers of oxidative stress may be modified by several mechanisms after feeding rats with complex dietary factors and that both pro- and antioxidant effects may consequently be observed simultaneously after short-term feeding of antioxidant-rich foods, herb medicines, or known pro- and antioxidants.
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PMID:Commonly consumed and naturally occurring dietary substances affect biomarkers of oxidative stress and DNA damage in healthy rats. 1520 83

The protective effect of Hsian-tsao (Mesona procumbens Hemsl.) and its active compounds on liver damage was evaluated using the model of tert-butyl hydroperoxide (t-BHP)-induced acute hepatic damage in rats. Male Sprague-Dawley rats (200 +/- 10 g) were orally pretreated with a water extract of Hsian-tsao (WEHT) (0.1, 0.5, and 1.0 g/kg) or caffeic acid (0.1 g/kg of body weight) for 13 days before a single dose of t-BHP (0.2 mmol/kg, intraperitoneally) to each animal, and the rats were sacrificed 18 h later by decapitation; blood samples were collected for the assays of serum biochemical values. The livers were excised from the animals and assayed for oxidative injury, antioxidant enzyme, and pathological histology. The result showed that the oral pretreatment of WEHT (0.1, 0.5, and 1.0 g/kg) or caffeic acid (0.10 g/kg) before t-BHP (0.2 mmol/kg) treatment significantly lowered the serum levels of the hepatic enzyme markers (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) and reduced oxidative stress of the liver by evaluation of malondialdehyde, glutathione, 8-hydroxy-2'-deoxyguanosine, glutathione peroxidase, and glutathione reductase. The histopathological evaluation of the rat livers showed that WEHT and caffeic acid reduced the incidence of liver lesions including cloudy swelling, pyknosis, and cytolysis induced by t-BHP in rats. On the basis of the results of this study, it can be speculated that M. procumbens protects liver against t-BHP-induced hepatic damage in rats.
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PMID:Protective effect of Mesona procumbens against tert-butyl hydroperoxide-induced acute hepatic damage in rats. 1521 57


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