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)

Preexposure of male Lewis rats to Cd aerosols (1.6 mg Cd/m3, 3 hr/day, 5 days/week, for 4 weeks) has been found to produce a marked degree of tolerance to hyperoxia (greater than 96% O2). Cd-pretreated animals were still alive after 8 days of continuous exposure to oxygen. In contrast, hyperoxia was fatal to all air-preexposed animals within 54-62 hr. Lungs of Cd-pretreated animals were characterized by hyperplasia and/or hypertrophy of the type II alveolar cell compartment which may have enabled them to more rapidly repair oxidant damage resulting from hyperoxia. Cd pretreatment augmented enzymatic antioxidant enzyme activities, including total lung Se-dependent glutathione peroxidase, catalase, glutathione reductase, and Mn-superoxide dismutase, and caused elevations in pulmonary nonprotein thiols and metallothionein (MT). MT, a thiol-rich, low-molecular-weight protein, was 400-fold higher in Cd-pretreated animals and bound more than 80% of the total Cd in the lung. We have hypothesized that MT serves as an expendable yet renewable cellular target for free radical damage during oxygen exposure. A systemic acute-phase response, characterized by alterations in plasma Zn and Cu concentrations and increased ceruloplasmin oxidase activity, was initiated in Cd-pretreated animals by the fourth day of hyperoxia. This response was accompanied by improvement in pulmonary status and extensive pulmonary repair.
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PMID:Cross-tolerance to hyperoxia following cadmium aerosol pretreatment. 233 May 88

The essential nutrients zinc (Zn) and selenium (Se) provide an antioxidant function to animal cells by very different mechanisms. Se is an integral part of Se-dependent glutathione peroxidases, a group of water-soluble enzymes that catalyze the destruction of water-soluble and, in some cases, membrane-bound hydroperoxides. In dietary Se deficiency, Se-dependent glutathione peroxidase activities are decreased; at Se intakes above that which is required for optimal growth, there is a slight to moderate increase in Se-dependent glutathione peroxidase activities. Because of the enzymatic nature of the major role of Se as an antioxidant, Se can be categorized as having a general antioxidant function, controlling peroxide levels in cells by degrading hydroperoxides. On the other hand, Zn functions as an antioxidant only at specific sites, and is not a required cofactor for an antioxidant enzyme. Although Zn plays a structural role in the enzyme Cu, Zn superoxide dismutase, the activity of this enzyme is not decreased in Zn deficiency and its activity is usually depressed at high Zn intakes. Zn may function as a site-specific antioxidant by two mechanisms. Firstly, it competes with Fe and Cu for binding to cell membranes and some proteins, displacing these redox-active metals and making them more available for binding to ferritin and metallothionein, respectively. Secondly, Zn binds the sulfhydryl groups in proteins, protecting them from oxidation. Zn status does not directly control tissue peroxide levels but can protect specific molecules against oxidative and peroxidative damage.
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PMID:Zinc and selenium, site-specific versus general antioxidation. 831 37

Glutathione has been implicated to function in cytoprotection against cadmium toxicity. The mechanism by which glutathione plays this role has not been well understood. Because glutathione is an important antioxidant and several studies have shown that cadmium induces oxidative stress, this study was undertaken to determine whether development of cadmium resistance is linked to enhanced antioxidant activities. A cadmium-resistant subpopulation of human lung carcinoma A549 cells, which was developed by repeatedly exposing the cells to step-wise increased cadmium concentrations, was compared to a cadmium-sensitive one. The acquired cadmium resistance resulted from neither decreased cadmium uptake nor enhanced cellular metallothionein synthesis. Glutathione content, however, was markedly elevated in the cadmium-resistant cells. In contrast, the activities of the glutathione redox cycle related enzymes, glutathione peroxidase and reductase, were unchanged. Two other antioxidant enzymes, superoxide dismutase and catalase, were also not altered. The results suggest that the development of cadmium resistance in A549 cells unlikely results from enhanced antioxidant enzyme activities, although it is associated with elevated cellular glutathione levels. In addition, measurement of the mRNA and DNA levels for gamma-glutamylcysteine synthetase, the rate-limiting enzyme for glutathione biosynthesis, revealed that enhanced expression of the enzyme but not gene amplification is likely responsible for the elevation of cellular glutathione levels.
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PMID:Cadmium resistance in A549 cells correlates with elevated glutathione content but not antioxidant enzymatic activities. 858 53

Cross-resistance presents an obstacle in cancer chemotherapy. Cadmium is a potential carcinogen whose exposure has been shown in epidemiological and laboratory experiments to cause lung cancer. Cadmium also induces various forms of resistance in human lung carcinoma cells. This resistance may be shared by antineoplastic agents, which should be a concern for chemotherapy of cadmium-induced lung cancer. In the present study, two subpopulations of human lung carcinoma A549 cells with a different magnitude of resistance to cadmium toxicity were shown to have a parallel resistance to the cytotoxic action of Adriamycin (ADR), an important anticancer drug. Several factors were examined to investigate the mechanism(s) for the cross-resistance, including cellular metallothionein and glutathione (GSH) concentrations, glutathione S-transferase activity, mdr1 expression, and antioxidant enzyme activities including superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Only cellular GSH content was elevated consistently in the cadmium/ADR-resistant cells relative to the cadmium/ADR-sensitive cells. Treatment with buthionine sulfoximine, a specific inhibitor of GSH synthesis sensitized both cell lines to ADR only when the cellular GSH levels were depleted to about 5% of control. This BSO treatment, however, did not affect cell viability. Further study revealed that the cadmium/ADR-resistant cells have a greater capacity in recovery of cellular GSH content following BSO treatment. The results demonstrate that cross-resistance to ADR exists in cadmium-resistant human lung carcinoma A549 cells, and enhanced GSH synthesis capacity, rather than elevated levels of cellular GSH, may be related to this resistance.
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PMID:Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells. 911 95

The mechanism of cadmium-mediated hepatotoxicity has been the subject of numerous investigations, principally in hepatocytes. Although, some uncertainties persist, sufficient evidence has emerged to provide a reasonable account of the toxic process in parenchymal cells. However, there is no information about the effect of cadmium in other hepatic cell types, such as stellate cells (fat storing cells, Ito cells, perisinusoidal cells, parasinusoidal cells, lipocytes). Hepatic stellate cells (HSC) express a quiescent phenotype in a healthy liver and acquire an activated phenotype in liver injury. These cells play an important role in the fibrogenic process. The objective of this study was to investigate the effect of a 24 h treatment of low Cd concentrations in glutathione content, lipid peroxidation damage, cytosolic free Ca, antioxidant enzyme activities: glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase along with the capacity of this heavy metal to induce metallothionein II and alpha(1)collagen (I) in an hepatic stellate cell line (CFSC-2G). Cd-treated cells increased lipid peroxidation and the content of cytosolic free calcium, decreased glutathione content and superoxide dismutase, glutathione peroxidase and catalase activity. Cd was able to induce the expression of the metallothionein II and alpha(1)collagen (I) gene, that was not described in this cell type. Cadmium may act as a pro-fibrogenic agent in the liver probably by inducing oxidative damage by enhancing lipid peroxidation and altering the antioxidant system of the cells. Although, the exact role metallothionein induction plays in this process is unknown, it probably, provides a cytosolic pool of potential binding sites to sequester ionic Cd, thereby decreasing its toxicity.
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PMID:Cadmium induces alpha(1)collagen (I) and metallothionein II gene and alters the antioxidant system in rat hepatic stellate cells. 1175 84

Antioxidants play a critical role in keeping skin healthy. The antioxidant benefits of vitamin C and E are well known, but the importance of the trace mineral, zinc, has been overlooked. This article reviews the evidence supporting zinc's antioxidant role in protecting against free radical-induced oxidative damage. Zinc protects against UV radiation, enhances wound healing, contributes to immune and neuropsychiatric functions, and decreases the relative risk of cancer and cardiovascular disease. All body tissues contain zinc; in skin, it is five to six times more concentrated in the epidermis than the dermis. Zinc is required for the normal growth, development and function of mammals. It is an essential element of more than 200 metalloenzymes, including the antioxidant enzyme, superoxide dismutase, and affects their conformity, stability, and activity. Zinc also is important for the proper functioning of the immune system, and for glandular, reproductive and cell health. Abundant evidence demonstrates the antioxidant role of zinc. Topical zinc, in the form of divalent zinc ions, has been reported to provide antioxidant photoprotection for skin. Two antioxidant mechanisms have been proposed for zinc: zinc ions may replace redox active molecules, such as iron and copper, at critical sites in cell membranes and proteins; alternatively, zinc ions may induce the synthesis of metallothionein, sulfhydryl-rich proteins that protect against free radicals. No matter how they work, topical zinc ions may provide an important and helpful antioxidant defense for skin.
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PMID:Evidence supporting zinc as an important antioxidant for skin. 1235 35

The effect of oral zinc (Zn) treatment was studied in the liver, kidneys and intestine of Long-Evans Cinnamon (LEC) rats in relation to metals interaction and concentration of metallothionein (MT) and glutathione (GSH). We also investigated the change in the activity of antioxidant enzymes and determined the biochemical profile in the blood and metal levels in urine. We showed that the Zn-treated group had higher levels of MT in the hepatic and intestinal cells compared to both untreated and basal groups. Tissue Zn concentrations were significantly higher in the Zn-treated group compared to those untreated and basal, whereas Cu and Fe concentrations decreased. The antioxidant enzyme activities in the Zn-treated group did not change significantly with respect to those in the basal group, except for hepatic glutathione peroxidase activity. Moreover, the biochemical data in the blood of Zn-treated group clearly ascertain no liver damage. These observations suggest an important role for Zn in relation not only to its ability to compete with other metals at the level of absorption in the gastrointestinal tract producing a decrease in the hepatic and renal Cu and Fe deposits, but also to MT induction as free radical scavenger.
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PMID:Effect and possible role of Zn treatment in LEC rats, an animal model of Wilson's disease. 1252 12

Because oxidative stress is involved in arterial hypertension, impairment of hepatic antioxidant defences could develop in the course of this disease. Metallothionein (MT), an antioxidant protein, is present in high rates in the liver. The aim of this study was to investigate the effect of a mineralocorticoid-salt treatment on blood pressure, hepatic antioxidant enzyme activities, and cardiac MT levels in transgenic MT null mice compared with control mice to further clarify the role of MT during the experimental development of arterial hypertension. Control and transgenic MT -/- mice were submitted to an 8-week mineralocorticoid-salt treatment. Hepatic glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase activities and cardiac MT and mineral levels were measured. Mineralocorticoid-salt treatment induced an increase in blood pressure in both transgenic MT -/- and control mice that was associated with an impairment of liver antioxidant status. MT deficiency was associated with modifications of hepatic antioxidant enzyme activities and with a decrease in cardiac iron levels. Adaptive processes of antioxidant systems may explain the absence of an effect of metallothionein deficiency on the development of mineralocorticoid-salt hypertension. The interactions that occur between the in vivo antioxidant systems probably produce a complex regulation of the oxidative balance and consequently prevent antioxidant deficiency.
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PMID:Antioxidant status in the liver of hypertensive and metallothionein-deficient mice. 1460 9

Saccharomyces cerevisiae mutant strains deficient in superoxide dismutase (Sod), an antioxidant enzyme, were used to analyze cadmium absorption and the oxidation produced by it. Cells lacking the cytosolic Sod1 removed twice as much cadmium as the control strain, while those deficient in the mitochondrial Sod2 exhibited poor metal absorption. Interestingly, the sod1 mutant did not become more oxidized after exposure to cadmium, as opposed to the control strain. We observed that the deficiency of Sod1 increases the expression of both Cup1 (a metallothionein) and Ycf1 (a vacuolar glutathione S-conjugate pump), proteins involved with protection against cadmium. Furthermore, when sod1 cells were exposed to cadmium, the ratio glutathione oxidized/glutathione reduced did not increase as expected. We propose that a high level of metallothionein expression would relieve glutathione under cadmium stress, while an increased level of Ycf1 expression would favor compartmentalization of this metal into the vacuole. Both conditions would reduce the level of glutathione-cadmium complex in cytosol, contributing to the high capacity of absorbing cadmium by the sod1 strain. Previous results showed that the glutathione-cadmium complex regulates cadmium uptake. These results indicate that, even indirectly, metallothionein also regulates cadmium transport.
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PMID:The effect of superoxide dismutase deficiency on cadmium stress. 1499 74

The aim of this work was to evaluate the potential utility of several biochemical parameters as indicators of the toxic effects of cadmium in the freshwater clam Corbicula fluminea under two levels of oxygenation (normoxia 21 kPa and hypoxia 4 kPa). These variations in oxygenation are representative of the natural environments of bivalves living at the bottom of the water column, where hypoxic episodes may occur regularly. Cadmium accumulation, metallothionein synthesis, MXR protein induction, lipoperoxidation and antioxidant enzyme activities (catalase, glutathione reductase and total and selenium-dependent glutathione peroxidases) were assessed in the gills of C. fluminea in four experimental conditions: normoxia, hypoxia, normoxia with cadmium and hypoxia with cadmium ([Cd]=30 microg l(-1)) over a 14-day period. Behavioural reactions were also followed for the duration of the experiment by monitoring clam activity and valve movements. This study is a first report on biochemical responses under cadmium contamination and hypoxia and will enable us to determine better biomarkers for C. fluminea as they were measured simultaneously. In metal-exposed animals, we found an increasing accumulation of cadmium in the gills with time, and this was more severe in hypoxic conditions. Metallothionein synthesis occurred in contaminated clams and was precocious in hypoxic conditions. MXR protein induction appeared promising due to its quick and significant response to metal with a strong impact from hypoxic contamination. On the other hand, in our experimental conditions, antioxidant parameters did not show decisive responses to contamination and hypoxia, except glutathione peroxidases which decreased systematically with time in a cadmium-independent manner. Lipid peroxidation, expressed as malondialdehyde content, was not stimulated by normoxic contamination, as has been shown in other studies, but was stimulated under hypoxic cadmium contamination. Our study confirms the importance of a multi-biomarker approach in environmental studies as some are not appropriate to all organisms.
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PMID:Impact of cadmium contamination and oxygenation levels on biochemical responses in the Asiatic clam Corbicula fluminea. 1604 Jan 39


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