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

A reproducible scheme has been developed for the preparation of rat liver thioredoxin and thioredoxin reductase (EC 1.6.4.5) by using assays based on reduction of insulin and 5,5'-dithiobis(2-nitrobenzoic acid), respectively. Both proteins were purified to homogeneity, as judged from polyacrylamide gel electrophoresis. Thioredoxin had a molecular weight of 12 000 and contained about 110 amino acids including 4 half-cystines and an NH2-terminal valine. Peptide maps of reduced and carboxymethylated thioredoxin showed that the protein had the active center sequence -Cys-Gly-Pro-Cys-Lys-Met- characteristic of thioredoxins also from procaryotes. Prolonged air oxidation of fully reduced thioredoxin created inactive, aggregated disulfide-containing molecules. Thioredoxin reductase showed a subunit molecular weight of 58 000 and a native molecular weight of 116 000. The enzyme was highly specific for NADPH with a Km of 6 microM. It contained FAD as prosthetic group and was sensitive to inhibition by arsenite. Thioredoxin reductase had a Km of 2.5 microM for rat and calf liver thioredoxin and a Kcat of 3000 min-1.
 ...
PMID:Rat liver thioredoxin and thioredoxin reductase: purification and characterization. 715 51

Methionine is converted by the transmethylation/transsulfuration pathway to homocysteine which may exert atherogenic effects by several mechanisms, including lipid peroxidation. Therefore, the excessive dietary methionine may induce the development of atherosclerosis. To test this hypothesis, plasma and aortic thiobarbituric acid reactive substances (TBARS), as well as activities of aortic and erythrocyte superoxide dismutase (SOD), catalase and selenium-dependent glutathione peroxidase (GPX) were measured in rabbits fed a diet enriched with 0.3% methionine for 6 or 9 months. Histological examinations of aortas also were performed. Feeding rabbits a methionine-enriched diet for 6 or 9 months resulted in significant increases in plasma and aortic TBARS levels and aortic antioxidant enzyme activities. However, a decrease in plasma antioxidant activity (AOA) was observed. In erythrocytes, SOD activity increased, catalase remained normal and GPX decreased in the treated animals. Histological examination of aortas showed typical atherosclerotic changes, such as intimal thickening, deposition of cholesterol, and calcification in methionine-fed rabbits. These results confirm that high-methionine diet may induce atherosclerosis in rabbits and indicate disturbances in lipid peroxidation and antioxidant processes as possible mechanisms of its atherogenic influence.
 ...
PMID:Increased lipid peroxidation as a mechanism of methionine-induced atherosclerosis in rabbits. 766 80

Protein synthesis and antioxidant enzyme activities were investigated in gamma-irradiated (300 Gy) and heat shocked (42 degrees C) larval stages of the gastrointestinal parasite, Heligmosomoides polygyrus bakeri (H. polygyrus). No qualitative or quantitative differences were observed in the incorporation of (35S)-methionine into somatic proteins of unirradiated or irradiated exsheathed third-stage (L3) larvae at either 37 degrees C or 42 degrees C. The rate of protein synthesis doubled in L3 stages maintained at 42 degrees C compared with 37 degrees C, irrespective of whether the larvae had been irradiated or not. The composition of excretory/secretory (ES) proteins varied between unirradiated and irradiated exsheathed L3 larvae maintained under identical conditions. Prominent heat-inducible proteins of 26 and 17 kDa were synthesised and excreted at 42 degrees C by both unirradiated and irradiated L3 stages. No major differences in protein synthesis could be detected between unirradiated and irradiated fourth-stage (L4) larvae. Temperature elevation significantly reduced protein synthesis in L4 stages, most notably in unirradiated parasites. Heat-inducible proteins were not detected in response to either irradiation or temperature elevation in L4 larvae. Immune sera recognised a similar spectrum of antigens in both unirradiated and irradiated L4 somatic and ES preparations and reacted with antigens from irradiated L4 parasites with less intensity than with antigens from unirradiated L4 larvae. Catalase was the only antioxidant enzyme examined with activity that changed significantly in irradiated parasites, being reduced to approximately 36% of normal levels in irradiated L4 stages. No significant difference existed between irradiated and unirradiated parasites in the levels of activity of superoxide dismutase and glutathione reductase.
 ...
PMID:The effect of gamma-radiation and heat shock on protein synthesis and antioxidant enzymes in the gastrointestinal parasite, Heligmosomoides polygyrus. 877 22

The liver is especially susceptible to the toxic effects of methionine due to its role in sulfur amino acid metabolism. Therefore, the excessive amounts of this amino acid may induce liver damage. To test the mechanisms of methionine-related hepatotoxicity, liver thiobarbituric acid reactive substances (TBARS), and activities of superoxide dismutase, catalase and selenium-dependent glutathione peroxidase were measured in rabbits fed a methionine-enriched diet for 6 or 9 mo. Morphological studies of livers were also made. Feeding rabbits the methionine-enriched diet for 9 mo resulted in a significant increase in liver TBARS levels and antioxidant enzyme activities. Moreover, an inflammatory infiltration of portal triads in the treated rabbits were observed. These results indicate that methionine may induce hepatitis by increasing free radical processes.
 ...
PMID:Increased lipid peroxidation and antioxidant activity in methionine-induced hepatitis in rabbits. 887 49

This study was conducted to observe the effects of endurance exercise training on antioxidant enzyme activity in the liver and gastrocnemius muscle of rats being fed dietary casein and soy protein. The respective influences of dietary casein and soy protein on the activity of antioxidant enzymes were also compared. Thirty-nine male Wistar rats, aged 3 weeks, were randomly assigned to six groups: a normal protein control group, a normal protein endurance training group, a casein protein control group, a casein protein endurance training group, a soy protein control group, and a soy protein endurance training group. The endurance exercise training groups were adapted to a treadmill for 2 weeks prior to the date the rats were forced to run for 60 min at 25 m/min, 5 days/week for 12 weeks. We found that antioxidant enzyme activity in the gastrocnemius muscle was neither effected by the dietary proteins (casein and soy protein) nor by the above endurance exercise training load. However, hepatic Cu,Zn-SOD activity increased significantly for the dietary casein and soy protein diet groups as compared with the normal protein diet group (P < 0.01). Furthermore, significant increases both in hepatic Cu,Zn-SOD activity in the normal protein group and hepatic GSHpx activity in the casein and soy protein groups were observed when rats were loaded with 25 m/min of endurance exercise training (P < 0.01). These results suggest that, under the above experimental conditions, a casein or soy protein diet increase hepatic Cu,Zn-SOD activity, while endurance exercise training is effective in increasing hepatic Cu;Zn-SOD activity on a normal protein diet and in increasing hepatic GSHpx activity for cysteine and methionine deficient diets.
 ...
PMID:Antioxidant enzymes response to endurance exercise training and dietary proteins in rat skeletal muscle and liver. 897 3

The deficiency of methionine, an essential amino acid, is associated with cardiovascular lesions. Because different types of cardiac pathologies are caused by a decrease in antioxidants, we examined the effects of methionine on myocardial antioxidant enzymes in hemodynamically assessed rats that were treated with methionine (10 mg/ml) in drinking water for 12, 24, and 48 h. Glutathione peroxidase (GSHPx) activity was significantly increased to 150.5 +/- 12.2 and 191.7 +/- 13.7% of the control value at 12 and 24 h, respectively, followed by a decline to 120 +/- 24.6% at 48 h. The mRNA levels of GSHPx at these time points were 151.2 +/- 12.0, 218.7 +/- 35.3, and 173.5 +/- 25.2%, respectively. Superoxide dismutase (SOD) activity was 144.3 +/- 3.7, 114.3 +/- 10.1, and 143.1 +/- 11. 2% at 12, 24, and 48 h, respectively. Catalase (Cat) activity was 272.4 +/- 5.4, 237.8 +/- 16.6, and 224.1 +/- 17.3% of the control value. The expression of Cat and SOD mRNA was unchanged at 12, 24, and 48 h. The lipid peroxidation was decreased by 24.4 +/- 11.2, 54. 9 +/- 0.1, and 6.4 +/- 2.1% at 12, 24, and 48 h, respectively. Methionine had no effect on the ventricular or aortic pressures, heart rate, and myocardial glutathione levels at any of the time points. The study shows that methionine has a significant effect on the myocardial antioxidant enzyme activities, and only changes in GSHPx enzyme activity correlated with the mRNA changes. These antioxidant changes may have a role in the beneficial effects of methionine in pathological rather than physiological conditions.
 ...
PMID:Effects of methionine on endogenous antioxidants in the heart. 1060 Aug 29

Thioredoxin, thioredoxin reductase and NADPH, the thioredoxin system, is ubiquitous from Archea to man. Thioredoxins, with a dithiol/disulfide active site (CGPC) are the major cellular protein disulfide reductases; they therefore also serve as electron donors for enzymes such as ribonucleotide reductases, thioredoxin peroxidases (peroxiredoxins) and methionine sulfoxide reductases. Glutaredoxins catalyze glutathione-disulfide oxidoreductions overlapping the functions of thioredoxins and using electrons from NADPH via glutathione reductase. Thioredoxin isoforms are present in most organisms and mitochondria have a separate thioredoxin system. Plants have chloroplast thioredoxins, which via ferredoxin-thioredoxin reductase regulates photosynthetic enzymes by light. Thioredoxins are critical for redox regulation of protein function and signaling via thiol redox control. A growing number of transcription factors including NF-kappaB or the Ref-1-dependent AP1 require thioredoxin reduction for DNA binding. The cytosolic mammalian thioredoxin, lack of which is embryonically lethal, has numerous functions in defense against oxidative stress, control of growth and apoptosis, but is also secreted and has co-cytokine and chemokine activities. Thioredoxin reductase is a specific dimeric 70-kDa flavoprotein in bacteria, fungi and plants with a redox active site disulfide/dithiol. In contrast, thioredoxin reductases of higher eukaryotes are larger (112-130 kDa), selenium-dependent dimeric flavoproteins with a broad substrate specificity that also reduce nondisulfide substrates such as hydroperoxides, vitamin C or selenite. All mammalian thioredoxin reductase isozymes are homologous to glutathione reductase and contain a conserved C-terminal elongation with a cysteine-selenocysteine sequence forming a redox-active selenenylsulfide/selenolthiol active site and are inhibited by goldthioglucose (aurothioglucose) and other clinically used drugs.
 ...
PMID:Physiological functions of thioredoxin and thioredoxin reductase. 1101 61

The mitochondrial antioxidant enzyme manganese-containing superoxide dismutase (MnSOD) functions as a tumor suppressor gene. Reconstitution of MnSOD expression in several human cancer cell lines leads to reversion of malignancy and induces a resistant phenotype to the cytotoxic effects of TNF and hyperthermia. The signaling pathways that underlie these phenotypic changes in MnSOD-overexpressing cells are unknown, although alterations in the activity of several redox-sensitive transcription factors, including AP-1 and NF-kappaB, have been observed. To determine the downstream signaling molecules involved in MnSOD-induced cell resistant phenotype, in the present study we analyzed the expression profile of several groups of genes related to stress response, DNA repair, and apoptosis, in a human breast cancer MCF-7 cell line overexpressing MnSOD (MCF+SOD). Of 588 genes examined, 5 (0.85%) were up-regulated (2-42-fold), and 11 (1.9%) were down-regulated (2-33-fold) in the MCF+SOD cells compared to the parental MCF-7 cells. The five up-regulated genes were MET, GADD153, CD9, alpha-catenin and plakoglobin. The genes with the most significant down-regulation included: vascular endothelial growth factor receptor 1, TNF-alpha converting enzyme, and interleukin-1beta. GADD153 (involved in the repair of DNA double strand breaks) showed a 33-fold increase in microarray analysis and these results were confirmed by RT-PCR. To further determine the specificity in MnSOD-induced gene regulation, MCF+SOD cells were stably transfected with an antisense MnSOD sequence whose expression was controlled by a tetracycline-inducible regulator. Expression of three up-regulated genes was measured after induction of antisense MnSOD expression. Interestingly, expression level of GADD153 but not MET or CD9 was reduced 24 h after antisense MnSOD induction. Together, these results suggest that reconstitution of MnSOD in tumor cells can specifically modulate the expression of down-stream effector genes. GADD153 and other elements observed in the MCF+SOD cells may play a key role in signaling the MnSOD-induced cell phenotypic change.
 ...
PMID:Genes regulated in human breast cancer cells overexpressing manganese-containing superoxide dismutase. 1116 72

The purpose of this study was to investigate whether cholesterol plus methionine feeding may be a convenient model to produce atherosclerosis in rats, and also to examine the contribution of oxidative stress to this development. For this reason, lipid peroxide levels and antioxidant enzyme activities in the liver and aorta as well as histopathological findings were determined in male Wistar-albino rats fed a diet supplemented with cholesterol plus cholic acid and methionine for six months. This diet was found to increase lipid peroxide levels in the liver of rats. Hepatic glutathione peroxidase (GSH-Px) and catalase (CAT) activities increased, but superoxide dismutase (SOD) activity remained unchanged. In conclusion, cholesterol and methionine feeding in rats did not cause oxidative stress and atherosclerotic changes in the aorta, although hepatic prooxidant-antioxidant balance was affected by this diet.
 ...
PMID:Cholesterol plus methionine feeding do not induce lipid peroxidation and atherosclerotic changes in the rat aorta. 1194 95

D-methionine (D-met) protects against cisplatin (CDDP) ototoxicity, but the mechanisms are not well understood. This study investigated D-met protection of cochlear oxidative state as measured by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and malondiadehyde (MDA) levels. The design comprised four groups of five rats each: (1) a saline control group, (2) a CDDP-only-treated group, (3) a CDDP group pretreated with D-met, and (4) a group receiving only D-met. Auditory brainstem response testing (ABR) was performed before and 3 days after injection. CDDP alone caused marked hearing loss; significantly reduced SOD, CAT, and GR levels; and increased MDA levels, but D-met pretreatment protected against these changes. These studies suggest that D-met protects cochlear antioxidant enzyme levels from CDDP-induced decrements. The excellent correlation of enzyme levels with hearing loss and weight loss suggests that antioxidant enzyme level protection may underlie, at least in part, D-met's otoprotective action.
 ...
PMID:The effect of D-methionine on cochlear oxidative state with and without cisplatin administration: mechanisms of otoprotection. 1285 39


1 2 3 4 5 Next >>