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)

Selenium is of fundamental importance to human health. It is an essential component of several major metabolic pathways, including thyroid hormone metabolism, antioxidant defence systems, and immune function. The decline in blood selenium concentration in the UK and other European Union countries has therefore several potential public health implications, particularly in relation to the chronic disease prevalence of the Western world such as cancer and cardiovascular disease. Ten years have elapsed since recommended dietary intakes of selenium were introduced on the basis of blood glutathione peroxidase activity. Since then 30 new selenoproteins have been identified, of which 15 have been purified to allow characterisation of their biological function. The long term health implications in relation to declining selenium intakes have not yet been thoroughly examined, yet the implicit importance of selenium to human health is recognised universally. Selenium is incorporated as selenocysteine at the active site of a wide range of selenoproteins. The four glutathione peroxidase enzymes (classical GPx1, gastrointestinal GPx2, plasma GPx3, phospholipid hydroperoxide GPx4)) which represent a major class of functionally important selenoproteins, were the first to be characterised. Thioredoxin reductase (TR) is a recently identified seleno-cysteine containing enzyme which catalyzes the NADPH dependent reduction of thioredoxin and therefore plays a regulatory role in its metabolic activity. Approximately 60% of Se in plasma is incorporated in selenoprotein P which contains 10 Se atoms per molecule as selenocysteine, and may serve as a transport protein for Se. However, selenoprotein-P is also expressed in many tissues which suggests that although it may facilitate whole body Se distribution, this may not be its sole function. A second major class of selenoproteins are the iodothyronine deiodinase enzymes which catalyse the 5'5-mono-deiodination of the prohormone thyroxine (T4) to the active thyroid hormone 3,3'5-triiodothyronine (T3). Sperm capsule selenoprotein is localised in the mid-peice portion of spermatozoa where it stabilises the integrity of the sperm flagella. Se intake effects tissue concentrations of selenoprotein W which is reported to be necessary for muscle metabolism. It is of great concern that the health implications of the decline in Se status in the UK over the past two decades have not been systematically investigated. It is well recognised that dietary selenium is important for a healthy immune response. There is also evidence that Se has a protective effect against some forms of cancer; that it may enhance male fertility; decrease cardiovascular disease mortality, and regulate the inflammatory mediators in asthma. The potential influence of Se on these chronic diseases within the European population are important considerations when assessing Se requirement.
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PMID:Selenium, selenoproteins and human health: a review. 1168 52

Comparative proteome analysis was performed between human normal (BEAS 2B) and malignant (A549) lung epithelial cells in an attempt to identify novel biomarkers of lung cancer. Approximately 500 protein spots could be separated by mini two-dimensional electrophoresis and visualized with Coomassie blue R-250. Among those relatively abundant proteins, eight spots were changed more than twofold reproducibly and identified by peptide mass fingerprints using mass spectrometry and database search. The increased proteins in A549 were aldehyde dehydrogenase, peroxiredoxin I, fatty acid binding protein, aldoketoreductase, and destrin, whereas the decreased proteins were galectin-1, transgelin, and stathmin. Since human lung is exposed to continuous oxidative stress, antioxidant enzyme peroxiredoxin I was selected for further investigation and its augmented expression was confirmed in cancer tissues compared to normal tissues from lung cancer patients, suggesting peroxiredoxin I as a potential biomarker of lung cancer.
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PMID:Augmented expression of peroxiredoxin I in lung cancer. 1171 2

In advanced cancer patients, the oxidative stress could take place either at the onset of disease or as a function of disease progression. To test this hypothesis, the following parameters were investigated: the erythrocyte activity of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), the serum activity of glutathione reductase (GR) and the serum total antioxidant status (TAS). The total antioxidant capacity of plasma LMWA was evaluated by the cyclic voltammetry methodology. We further determined the serum levels of proinflammatory cytokines (IL-6 and TNFalpha), IL-2, leptin and C-reactive protein (CRP). All of these parameters have been correlated with the most important clinical indices of patients such as Stage of disease, ECOG PS and clinical response. Eighty-two advanced stage cancer patients and 36 healthy individuals used as controls were included in the study. Our findings show that SOD activity was significantly higher in cancer patients than in controls and GPx activity was significantly lower in cancer patients than in controls. Serum values of IL-6, TNFalpha and CRP were significantly higher in patients than in controls. Serum leptin values of cancer patients were significantly lower than controls. SOD activity increased significantly from Stage II/ECOG 0-1 to Stage IV/ECOG 0-1, whereas it decreased significantly in Stage IV/ECOG 3. GPx activity decreased significantly in Stage IV/ECOG 2-3. An inverse correlation between ECOG PS and serum leptin levels was found. Serum levels of IL-2 decreased from Stage II/ECOG 0-1 to Stage IV/ECOG 2-3. A direct correlation between Stage/ECOG PS and serum levels of both IL-6 and CRP was observed. Cisplatin administration induced a significant increase of GPx after 24 hr. In conclusion, this is the first study that shows that several "biological" parameters of cancer patients such as antioxidant enzyme activity, cytokines, leptin and CRP strictly correlate with the most important clinical parameters of disease such as Stage and ECOG PS.
Int J Cancer 2002 Mar 01
PMID:Quantitative evaluation of oxidative stress, chronic inflammatory indices and leptin in cancer patients: correlation with stage and performance status. 1185 90

Copper zinc superoxide dismutase (CuZnSOD) is an essential primary antioxidant enzyme that converts superoxide radical to hydrogen peroxide and molecular oxygen in the cytoplasm. Cytosolic glutathione peroxidase (GPx) converts hydrogen peroxide into water. The overall goal of the present study was to explore the possible role of the antioxidant enzyme CuZnSOD in expression of the malignant phenotype. We hypothesized that overexpression of CuZnSOD would lead to the suppression of at least part of the human malignant phenotype. To test this hypothesis, human CuZnSOD cDNA was transfected into U118-9 human malignant glioma cells. CuZnSOD activity levels increased 1.5-, 2.0-, 2.6-, and 3.5-fold, respectively, in four table transfected cell lines compared with wild type and vector controls. Overexpression of CuZnSOD altered cellular antioxidant enzyme profiles, including those of manganese superoxide dismutase, catalase, and GPx. The transfected clone with the highest CuZnSOD:GPx ratio (3.5) showed a 42% inhibition of tumor cell growth in vitro. The decreased rate of tumor cell growth in vitro was strongly correlated with the enzyme activity ratio of CuZnSOD:GPx. Glioma cells that stably overexpressed CuZnSOD demonstrated additional suppressive effects on the malignant phenotype when compared with the parental cells and vector controls. These cells showed decreased plating efficiency, elongated cell population doubling time, lower clonogenic fraction in soft agar, and, more significantly, inhibition of tumor formation in nude mice. This work suggested that CuZnSOD is a new tumor suppressor gene. Increased intracellular ROS levels were found in cells with high activity ratios of CuZnSOD:GPx. Change in the cellular redox status, especially change attributable to the accumulation of hydrogen peroxide or other hydroperoxides, is a possible reason to explain the suppression of tumor growth observed in CuZnSOD-overexpressing cells.
Cancer Res 2002 Feb 15
PMID:Overexpression of copper zinc superoxide dismutase suppresses human glioma cell growth. 1186 5

NF-kappaB is known to exert a cytoprotective action against TNF-alpha-induced apoptosis. To study the role of NF-kappaB in various TNF-alpha-treated epithelial cell lines, we generated stable transfectants overexpressing a mutated unresponsive form of the IkappaBalpha inhibitor (MT cells). As NF-kappaB prevented TNF-alpha-induced apoptosis in various epithelial cancer cell lines, we searched for NF-kappaB target gene products responsible for this difference of sensitivity. We observed an increased Bcl-X(L) expression level in OVCAR-3 cells compared with OVCAR-3 cells expressing a mutated IkappaBalpha inhibitor (MT cells). Induction of the antioxidant enzyme MnSOD was detected only in TNF-alpha-treated OVCAR, MCF7A/Z and HCT116 cells but not in MT cells. Moreover, reactive oxygen species were involved in TNF-alpha-induced apoptosis, as various antioxidants partially protected these cells from apoptosis. At last, transfection of the MnSOD cDNA in MT cells, which do not express this protein after TNF-alpha stimulation, partially restored resistance to TNF-alpha-induced cell death, as observed by clonogenic assays. However, transfection of the Bcl-X(L) cDNA did not induce any protective effect. Therefore, MnSOD expression is induced by NF-kappaB in epithelial cancer cells in response to TNF-alpha, and is at least partially responsible for their resistance to TNF-alpha-induced apoptosis, presumably through the clearance of death-inducing ROS.
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PMID:NF-kappaB-dependent MnSOD expression protects adenocarcinoma cells from TNF-alpha-induced apoptosis. 1203 30

Manganese superoxide dismutase (MnSOD) has been shown to suppress the development of cancer. Tamoxifen (TAM), a nonsteroidal anti-estrogen that is widely used in chemotherapy, is known to be a modulator of antioxidant status. However, the mechanism by which TAM mediates antioxidant enzyme induction remains unclear. In this study we investigated TAM enhancement of MnSOD induction by TNF-alpha. The results show that co-treatment with TAM and TNF-alpha increases the MnSOD promoter/enhancer driven luciferase activity, MnSOD mRNA and protein levels. Interestingly, co-treatment with TAM and TNF-alpha drastically decreases the binding activity of the p50/p50 homodimer and increases that of the p50/p65 heterodimer compared to TNF-alpha alone. This change in DNA binding could not be attributed to a decrease in the level of p50, its precursor, p105, or its inhibitors. Furthermore, TAM did not enhance degradation of IkappaB-alpha. These results suggest that p50/p50 homodimer may act as an inhibitory complex of MnSOD expression. Modulation of the DNA binding activity in favor of the p50/p65 complex may enhance NF-kappaB mediated induction of MnSOD by TAM. These findings reveal a potential novel mechanism for the induction of the human MnSOD gene.
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PMID:Tamoxifen enhancement of TNF-alpha induced MnSOD expression: modulation of NF-kappaB dimerization. 1203 62

We measured the activities of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPX) before therapy in 97 patients with cancer in various sites (gastrointestinal tract (GIT) (n=40), breast (n=30), and others (n=27)), and in 60 matched controls to assess antioxidant enzyme protection. Hemolysate hemoglobin (Hb) was measured spectrophotometrically. The activity of SOD (U/g Hb) was significantly lower in all sites (when all the cancer sites were considered as a group), GIT, breast, and other sites compared to the controls (P<0.0001, P<0.0001, P<0.0001 and P<0.0001, respectively). The activity of GPX (U/g Hb) was significantly decreased in all sites, GIT, and breast cancer sites than in the controls (P=0.024, P=0.033, and P=0.043, respectively). Age showed a weak negative correlation with enzyme activities in controls and patients. There was no significant association between SOD and GPX activities in either the controls or the patients. These results suggest that there may be a greater antioxidant burden for SOD than GPX in cancer, and that a weak association exists between the activities of the two enzymes in antioxidant protection.
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PMID:Activities of erythrocyte antioxidant enzymes in cancer patients. 1211 88

Our recent study using serial analysis of gene expression show the decreased expression of glutathione peroxidase (GPx), an antioxidant enzyme, in an anaplastic carcinoma. To clarify the expression of GPx in various kinds of thyroid tumors, the expression levels of GPx mRNA in 79 benign and malignant thyroid tissues were measured by means of real-time quantitative reverse transcription-polymerase chain reaction. A decreased expression of GPx mRNA was observed in all of five anaplastic carcinomas and some of the papillary carcinomas. A molecular-based therapy which produces O(2) radical may be considered as an alternative choice for the treatment of anaplastic carcinomas.
Cancer Lett 2002 Aug 08
PMID:Decreased expression of glutathione peroxidase mRNA in thyroid anaplastic carcinoma. 1217 25

Through the induction of apoptosis, CD95 plays a crucial role in the immune response and the elimination of cancer cells. Ligation of CD95 receptor activates a complex signaling network that appears to implicate the generation of reactive oxygen species (ROS). This study investigated the place of ROS production in CD95-mediated apoptosis and the role of the antioxidant enzyme glutathione peroxidase-1 (GPx1). Anti-CD95 antibodies triggered an early generation of ROS in human breast cancer T47D cells that was blocked by overexpression of GPx1 and inhibition of initiator caspase activation. Enforced expression of GPx1 also resulted in inhibition of CD95-induced effector caspase activation, DNA fragmentation, and apoptotic cell death. Resistance to CD95-mediated apoptosis was not due to an increased expression of anti-apoptotic molecules and could be reversed by glutathione-depleting agents. In addition, whereas the anti-apoptotic protein Bcl-xL prevented CD95-induced apoptosis in MCF-7 cells, it did not inhibit the early ROS production. Moreover, Bcl-xL but not GPx1 overexpression could suppress the staurosporine-induced late generation of ROS and subsequent cell death. Altogether, these findings suggest that GPx1 functions upstream of the mitochondrial events to inhibit the early ROS production and apoptosis induced by CD95 ligation. Finally, transgenic mice overexpressing GPx1 were partially protected from the lethal effect of anti-CD95, underlying the importance of peroxide formation (and GPx1) in CD95-triggered apoptosis.
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PMID:Glutathione peroxidase-1 protects from CD95-induced apoptosis. 1222 Oct 75

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


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