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)

Heme, the iron-porphyrin coordination complex, released from the degradation of hemoproteins, is a strong prooxidant. It is enzymatically degraded by heme oxygenase to free iron, carbon monoxide and biliverdin. Biliverdin and its reduced metabolite bilirubin are two potent physiological antioxidants. Here we show a progressive increase of steady-state levels of the mRNA encoding the inducible isoform of this enzyme (heme oxygenase-1) in the rat liver during aging. We had previously reported that aging is associated with increased activation of the nuclear factor kappaB (NFkappaB). We now provide evidence to establish that overexpression of NFkappaB in transfected liver-derived HepG2 cells can cause a marked induction of the endogenous heme oxygenase-1 (HO-1) mRNA and activation of the cotransfected HO-1 gene promoter. Taken together, these results support the conclusion that enhanced oxidative stress during aging is accompanied by compensatory induction of the antioxidant enzyme HO-1 through activation of the NFkappaB pathway.
 ...
PMID:Age-dependent increase of heme oxygenase-1 gene expression in the liver mediated by NFkappaB. 1073 81

Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that reduces superoxide anion to hydrogen peroxide in cell mitochondria. MnSOD is overexpressed in normal aging brain and in various central nervous system disorders; however, the mechanisms mediating the upregulation of MnSOD under these conditions remain poorly understood. We previously reported that cysteamine (CSH) and other pro-oxidants rapidly induce the heme oxygenase-1 (HO-1) gene in cultured rat astroglia followed by late upregulation of MnSOD in these cells. In the present study, we demonstrate that antecedent upregulation of HO-1 is necessary and sufficient for subsequent induction of the MnSOD gene in neonatal rat astroglia challenged with CSH or dopamine, and in astroglial cultures transiently transfected with full-length human HO-1 cDNA. Treatment with potent antioxidants attenuates MnSOD expression in HO-1-transfected astroglia, strongly suggesting that intracellular oxidative stress signals MnSOD gene induction in these cells. Activation of this HO-1-MnSOD axis may play an important role in the pathogenesis of Alzheimer disease, Parkinson disease and other free radical-related neurodegenerative disorders. In these conditions, compensatory upregulation of MnSOD may protect mitochondria from oxidative damage accruing from heme-derived free iron and carbon monoxide liberated by the activity of HO-1.
 ...
PMID:Role of heme oxygenase-1 in the regulation of manganese superoxide dismutase gene expression in oxidatively-challenged astroglia. 1094 21

Antioxidant defense system prevents the organism from the detrimental effects of free radicals via scavenging or inhibiting their formation. Changes in the antioxidant defense mechanisms and alterations of several essential trace elements in both plasma and various tissues of ob/ob mice have been reported previously. Recent finding of the restoration of the defective antioxidant enzyme activity after leptin treatment in ob/ob mice suggests a putative role of leptin in modulation of antioxidant enzyme activity. Therefore, the aim of this study was to investigate whether antioxidant enzymes and trace elements could also be altered in patients with leptin gene mutation. Seven patients (five men and two women, two of them are homozygous and 5 are heterozygous) with leptin gene mutation and 31 healthy, sex- and age-matched and non-related to the patients (24 male and 9 female), control volunteers were enrolled in the study. Plasma and erythrocyte glutathione peroxidase (GSH-Px) and erythrocyte copper-zinc superoxide dismutase (CuZn-SOD) activities were measured spectrophotometrically. Plasma selenium (Se), manganese (Mn), zinc (Zn), copper (Cu), and iron (Fe) levels were measured by atomic absorption spectrophotometry. Mean Cu and Fe levels in patients were not significantly different than those in controls whereas mean Se, Zn and Mn levels were significantly lower in patients than those of controls (P=0.007, P=0.001, and P=0.001, respectively). Erythrocyte GSH-Px (39%), plasma GSH-Px (24%) and erythrocyte CuZn-SOD activities (32%) were significantly lower than those of the control group (P=0.001, P=0.002, P=0.001, respectively). In conclusion, our results demonstrate that the activity of antioxidant enzymes and plasma levels of Se, Zn and Mn levels were decreased in both homozygous and heterozygous subjects with leptin gene mutation. We suggest that both leptin and trace elements might be involved in the modulation of antioxidant defense system.
 ...
PMID:Defective antioxidant defense system in patients with a human leptin gene mutation. 1096 32

Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. Several antioxidants have been described as beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1, 10-dimethoxyaporphine) is a major alkaloid found in the leaves and bark of boldo (Peumus boldus Molina), and has been shown to possess antioxidant activity and anti-inflammatory effects. From this point of view, the possible anti-diabetic effect of boldine and its mechanism were evaluated. The experiments were performed on male rats divided into four groups: control, boldine (100 mg kg(-1), daily in drinking water), diabetic [single dose of 80 mg kg(-1)of streptozotocin (STZ), i.p.] and diabetic simultaneously fed with boldine for 8 weeks. Diabetic status was evaluated periodically with changes of plasma glucose levels and body weight in rats. The effect of boldine on the STZ-induced diabetic rats was examined with the formation of malondialdehydes and carbonyls and the activities of endogenous antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in mitochondria of the pancreas, kidney and liver. The scavenging action of boldine on oxygen free radicals and the effect on mitochondrial free-radical production were also investigated. The treatment of boldine attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. The levels of malondialdehyde (MDA) and carbonyls in liver, kidney and pancreas mitochondria were significantly increased in STZ-treated rats and decreased after boldine administration. The activities of mitochondrial manganese superoxide dismutase (MnSOD) in the liver, pancreas and kidney were significantly elevated in STZ-treated rats. Boldine administration decreased STZ-induced elevation of MnSOD activity in kidney and pancreas mitochondria, but not in liver mitochondria. In the STZ-treated group, glutathione peroxidase activities decreased in liver mitochondria, and were elevated in pancreas and kidney mitochondria. The boldine treatment restored the altered enzyme activities in the liver and pancreas, but not the kidney. Boldine attenuated both STZ- and iron plus ascorbate-induced MDA and carbonyl formation and thiol oxidation in the pancreas homogenates. Boldine decomposed superoxide anions, hydrogen peroxides and hydroxyl radicals in a dose-dependent manner. The alkaloid significantly attenuated the production of superoxide anions, hydrogen peroxide and nitric oxide caused by liver mitochondria. The results indicate that boldine may exert an inhibitory effect on STZ-induced oxidative tissue damage and altered antioxidant enzyme activity by the decomposition of reactive oxygen species and inhibition of nitric oxide production and by the reduction of the peroxidation-induced product formation. Boldine may attenuate the development of STZ-induced diabetes in rats and interfere with the role of oxidative stress, one of the pathogeneses of diabetes mellitus.
 ...
PMID:Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats. 1098 97

Autoxidation of globin chains and iron overload are the suggested mechanisms for the increased oxidative stress in beta-thalassemia. The aim of this study was to evaluate the extend of lipid peroxidation and antioxidant status of patients with beta-thalassemia and iron deficiency anemia (IDA) and compare the results with healthy subjects. Oxidant and antioxidant status of the children with beta-thalassemia major (n = 22) and iron deficiency anemia (n = 19) were studied. Healthy controls (n = 14) were age and sex matched. Fresh anticoagulated venous blood samples were obtained from all children. Conjugated diene (CD) and thiobarbituric acid-reactive (TBARS) substances were analyzed to indicate the oxidative parameters, whereas the erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured to show the antioxidant status of the children. Plasma TBARS and CD concentrations were elevated in beta-thalassemia compared to IDA. When compared to the controls, elevation in TBARS was significant. In the iron-deficiency group both TBARS and CD levels were decreased compared to the controls. SOD and GPx activities were increased in the beta-thalassemia group. SOD in beta-thalassemia was higher than both IDA and the controls and GPx activity was higher than the IDA group. In vivo lipid peroxidation was increased in children with beta-thalassemia major. This leads to a compensatory increase in antioxidant enzymes, whereas IDA does not lead to lipid peroxidation with a normal antioxidant enzyme activity.
 ...
PMID:Lipid peroxidation and antioxidant status in beta-thalassemia. 1112 1

Iron-overload cardiomyopathy is a restrictive cardiomyopathy that manifests itself as systolic or diastolic dysfunction secondary to increased deposition of iron in the heart and occurs with common genetic disorders such as primary hemochromatosis and beta-thalassemia major. Although the exact mechanism of iron-induced heart failure remains to be elucidated, the toxicity of iron in biological systems is believed to be attributed to its ability to catalyze the generation of oxygen-free radicals. In the current investigation, the dose-dependent effects of chronic iron-loading on heart tissue concentrations of iron, glutathione peroxidase (GPx) activity, free-radical production, and cardiac dysfunction were investigated in a murine model of iron-overload cardiomyopathy. It was shown that chronic iron-overload results in dose-dependent (a) increases in myocardial iron burden, (b) decreases in the protective antioxidant enzyme GPx activity, (c) increased free-radical production, and (d) increased mortality. These findings show that the mechanism of iron-induced heart dysfunction involves in part free radical-mediated processes.
 ...
PMID:Iron-overload cardiomyopathy: evidence for a free radical--mediated mechanism of injury and dysfunction in a murine model. 1123 11

The expression of the HIV-1 Tat protein in HeLa cells resulted in a 2.5-fold decrease in the activity of the antioxidant enzyme glutathione peroxidase (GPX). This decrease seemed not to be due to a disturbance in selenium (Se) uptake. Indeed, the intracellular level of Se was similar in parental and tat-transfected cells. A Se enrichment of the medium did not lead to an identical GPX activity in both cell lines, suggesting a disturbance in Se utilization. Total intracellular 75Se selenoproteins were analyzed. Several quantitative differences were observed between parental and tat-transfected cells. Mainly, cytoplasmic glutathione peroxidase and a 15-kDa selenoprotein were decreased in HeLa-tat cells, while phospholipid hydroperoxide glutathione peroxidase and low-molecular-mass selenocompounds were increased. Thioredoxin reductase activity and total levels of 75Se-labeled proteins were not different between the two cell types. The effect of Tat on GPX mRNA levels was also analyzed. Northern blots revealed a threefold decrease in the GPX/glyceraldehyde phosphate dehydrogenase mRNA ratio in HeLa-tat versus wild type cells. By deregulating the intracellular oxidant/antioxidant balance, the Tat protein amplified UV sensitivity. The LD50 for ultraviolet radiation A was 90 J/cm2 for HeLa cells and only 65 J/cm2 for HeLa-tat cells. The oxidative stress occurring in the Tat-expressing cells and demonstrated by the diminished ratio of reduced glutathione/oxidized glutathione was not correlated with the intracellular metal content. Cellular iron and copper levels were significantly decreased in HeLa-tat cells. All these disturbances, as well as the previously described decrease in Mn superoxide dismutase activity, are part of the viral strategy to modify the redox potential of cells and may have important consequences for patients.
 ...
PMID:Human immunodeficiency virus type 1 Tat protein impairs selenoglutathione peroxidase expression and activity by a mechanism independent of cellular selenium uptake: consequences on cellular resistance to UV-A radiation. 1136 44

We addressed the hypothesis that in vitro short-term exposure to hematite (Fe(2)O(3)) and polycyclic aromatic hydrocarbons (PAHs) is more deleterious by virtue of their combinations being able to cause higher oxidative stress conditions in human lung cells (A549), than either chemical alone. Lipid peroxidation (malondialdehyde; MDA), antioxidant enzyme activities (superoxide dismutase; SOD, glutathione peroxidase; GPx, glutathione reductase; GR), glutathione status (reduced glutathione; GSH, oxidized glutathione; GSSG) and alpha-tocopherol (alpha-Toc) consumption were studied in cells exposed to Fe(2)O(3), benzo(a)pyrene (B(a)P) or pyrene, alone or in association. We found that increases in GSSG/GSH (P<0.01) and in alpha-Toc consumption (P<0.01) counteracted Fe(2)O(3)-induced lipid peroxidation. Exposure to B(a)P did not induce oxidative injury because of the involvement of non-enzymatic antioxidants in cell homeostasis. Pyrene did not induce free radicals (FR)-induced injury. Exposure to PAHs-coated onto Fe(2)O(3) particles damaged both the enzymatic (i.e. increases in SOD and GR activities; P<0.01) and the non-enzymatic (i.e. increases in GSSG/GSH; P<0.001, alpha-Toc consumption; P<0.01) antioxidant defenses, thereby allowing lipid peroxidation (i.e. MDA production; P<0.05). Exposure to PAHs-coated onto Fe(2)O(3) particles induced not only higher lipid peroxidation (i.e. MDA production; P<0.05) but also higher antioxidant alterations (i.e. SOD and GR activities; P<0.05, GSSH/GSH; P<0.01 or P<0.05) than either chemical alone. Several mechanisms could account for this result, enhanced uptake of Fe(2)O(3) and/or greater availability of PAHs. Hence, our results indicate that exposure to PAHs-coated onto Fe(2)O(3) particles is more deleterious in lungs than either chemical alone.
 ...
PMID:Antioxidant defense disruption by polycyclic aromatic hydrocarbons-coated onto Fe(2)O(3) particles in human lung cells (A549). 1154 9

There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.
 ...
PMID:Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. 1155 12

Expression of superoxide dismutases (FeSOD and MnSOD) and catalases by laboratory strains of Pseudomonas aeruginosa is modulated by exogenous factors. Whether clinical isolates behave similarly and whether antioxidant enzyme expression influences P. aeruginosa virulence remain unclear. Fifty-seven P. aeruginosa blood culture isolates, plus seven pairs of blood and local-site isolates, were examined for FeSOD, MnSOD, and catalase production in vitro. Under iron-replete growth conditions FeSOD and catalase activities were maximized. MnSOD was not detected. FeSOD and catalase activity decreased under iron-limited growth conditions, whereas MnSOD activity appeared. SOD and catalase activity did not change with site of isolation or by patient. MnSOD could not be expressed by one isolate due to a missense mutation in sodA that produced a premature stop codon. Eleven percent of the isolates expressed a novel, rapidly migrating MnSOD that was associated with missense mutations in the normal stop codon of sodA. We conclude that clinical P. aeruginosa isolates vary little in FeSOD and catalase expression. Some strains produce a newly described MnSOD variant, whereas one is deficient in MnSOD production. The absence of MnSOD expression in a P. aeruginosa strain causing invasive human disease indicates that MnSOD is probably not essential for P. aeruginosa virulence.
 ...
PMID:Antioxidant enzyme expression in clinical isolates of Pseudomonas aeruginosa: identification of an atypical form of manganese superoxide dismutase. 1170 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>