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)

Dietary restriction (DR) is the only known intervention that delays aging and age-related diseases. Mechanisms proposed to explain this DR effect include a decline in free radical production and an increase in free radical detoxification. In the present study the effect of bleomycin (BLM) as a reactive oxygen species-generating antitumor drug has been evaluated on antioxidant enzymes and the electron transport system in different cellular fractions of liver in female and male Fischer 344 rats. Animals were fed ad libitum (AL) or 60% of the AL intake (DR) and were given a single intraperitoneal injection of 2.5, 5, or 10 mg BLM/kg body wt. After four weeks, BLM significantly increased glutathione peroxidase and lactate dehydrogenase activities in liver cytosol of female AL rats and increased activity even more in male rats. Similar changes were also noted for glutathione reductase and glucose 6-phosphate dehydrogenase activities in BLM-treated AL rats. In liver mitochondria, glutathione peroxidase was increased in female and male AL rats but was increased more in female rats. Drug treatment had no significant effect on these enzyme activities in cytosolic or mitochondrial fractions of DR animals. Profound effects of BLM were noted in activities of complexes I, III, and IV of the electron transport system in AL and DR female and male rats; however, complex II demonstrated no significant diet or treatment effect. Induced antioxidant enzyme activities in BLM-treated AL rats may be a response to excessive free radical generation due to BLM metabolism in AL animals that is mitigated by DR. Furthermore, dysfunction of the electron transport system might suggest its role in a secondary generation of free radicals during BLM metabolism contributing to its toxicity.
Nutr Cancer 2000
PMID:Effects of bleomycin on liver antioxidant enzymes and the electron transport system from ad libitum-fed and dietary-restricted female and male Fischer 344 rats. 1079 15

Evidence from a number of studies suggests that the mechanism by which tumor necrosis factor (TNF) kills transformed cells involves oxidative stress. NAD(P)H:(quinone acceptor) oxidoreductase (NQO1) is an antioxidant enzyme with particular relevance to cancer. The MCF-7 breast cancer cell line was stably transfected with rat NQO1 cDNA to determine whether increased NQO1 activity alters sensitivity to TNF-induced apoptosis. Five clones, with a range of NQO1 enzyme activities from 5- to 50-fold greater than the MCF-7 line, and two control transfectants were examined. Northern blot hybridization analyses and reverse transcription-PCR demonstrated that the increase in NQO1 activity in the transfectants was attributable to expression from the transfected rat sequence. Based on sulforhodamine B assays for the number of viable cells, the NQO1 clones showed increased sensitivity to EO9, an indoloquinone that undergoes bioactive reduction by NQO1. Viability studies also demonstrated that the NQO1 transfectants were significantly more sensitive to TNF than the control transfectants or MCF-7 parent. This increased sensitivity could not be explained by changes in superoxide dismutase or catalase activity or to increased sensitivity to oxidative stress in general, as assessed by response to hydrogen peroxide and paraquat treatment. Using dichlorodihydrofluorescein diacetate as a probe, we found that the NQO1 transfectants had no difference in baseline level of oxidative stress compared to the control cells but did exhibit greater intracellular oxidative stress after TNF treatment. We conclude that NQO1 can affect the TNF-mediated pathway to apoptosis.
Cancer Res 2000 Jul 01
PMID:Increased tumor necrosis factor-alpha sensitivity of MCF-7 cells transfected with NAD(P)H:quinone reductase. 1091 79

Manganese-containing superoxide dismutase (MnSOD) is an essential primary antioxidant enzyme that converts superoxide radical to hydrogen peroxide and molecular oxygen within the mitochondrial matrix. Cytosolic glutathione peroxidase (GPX) converts hydrogen peroxide into water. MnSOD is reduced in a variety of tumor types and has been proposed to be a new kind of tumor suppressor gene, but the mechanism(s) by which MnSOD suppresses malignancy is unclear. According to the enzymatic reactions catalyzed by MnSOD and cytosolic GPX, change in the cellular redox status, especially change attributable to accumulation of hydrogen peroxide or other hydroperoxides, is a possible reason to explain the suppression of tumor growth observed in MnSOD-overexpressing cells. To test this possible mechanism, we transfected human cytosolic GPX cDNA into human glioma cells overexpressing MnSOD. The results showed that GPX overexpression not only reversed the tumor cell growth inhibition caused by MnSOD overexpression but also altered the cellular contents of total glutathione, reduced glutathione, oxidized glutathione, and intracellular reactive oxygen species. Overexpression of GPX also inhibited degradation of the inhibitory subunit alpha of nuclear factor-KB. These results suggest that hydrogen peroxide or other hydroperoxides appear to be key reactants in the tumor suppression by MnSOD overexpression, and growth inhibition correlates with the intracellular redox status. This work suggests that manipulations that inhibit peroxide removal should enhance the tumor suppressive effect of MnSOD overexpression.
Cancer Res 2000 Jul 15
PMID:The role of cellular glutathione peroxidase redox regulation in the suppression of tumor cell growth by manganese superoxide dismutase. 1091 71

It has been reported that several cis-unsaturated fatty acids (c-UFAs) could increase doxorubicin (DOX) accumulation in cancer cells and hence elevate its cytotoxicity. However, some researchers showed that c-UFA pretreatment did not affect its cytotoxicity in special cell lines. It is possible that the different results occurred due to different cellular characteristics. We hypothesized that c-UFA treatment might modulate the activities of some antioxidant enzymes to affect the resistance of cells to DOX. In the present study, we examined how c-UFA pretreatment affected DOX cytotoxicity on mouse leukemia cell line, P388, and its resistant subline, P388/DOX, which we found to have significantly higher glutathione peroxidase (GPx) activity as well as P-glycoprotein (p-gp) overexpression. We chose two c-UFAs, gamma-linolenic acid (GLA) (18:3n-6) and docosahexaenoic acid (DHA) (22:6n-3). Cytotoxicity was measured by MTT (3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and trypan blue exclusion assays. DOX accumulation and p-gp expression were measured by flow cytometry. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and GPx were determined for both cell lines with and without treatment with GLA or DHA. Significant DOX accumulation occurred in both cell lines with GLA or DHA pretreatment, but without any change in p-gp expression in either cell line. Sensitivity to DOX cytotoxicity was improved by GLA or DHA pretreatment in P388/DOX in which only SOD activity was significantly increased, but not in the parental cell line P388 in which both SOD and CAT were significantly increased by the pretreatment. However, combined pretreatment of GLA or DHA with antioxidants, pyrrolidinedithiocarbamate (PDTC) or Vitamin C, could sensitize not only P388/DOX but also P388 cells to DOX. We conclude that the effects of c-UFA pretreatment on the sensitivity of cancer cells to DOX not only depend on the change in drug accumulation but also the change in the levels of antioxidant enzyme activities, and suggest that combined administration of c-UFAs, antioxidants, and DOX may be more effective in treating leukemia.
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PMID:Effects of cis-unsaturated fatty acids on doxorubicin sensitivity in P388/DOX resistant and P388 parental cell lines. 1095 54

Because of their antioxidant properties, carotenoids may have beneficial effects in preventing cancer and cardiovascular disease. However, in humans consuming carotenoid-rich vegetables, data concerning the antioxidant effects of carotenoids are rather scarce. A human intervention trial was conducted, therefore, to determine whether a moderately increased consumption of carotenoid-rich vegetables would influence the antioxidant status in 23 healthy men. This short-term feeding study lasted 8 wk during which the men consumed a low carotenoid diet. A 2-wk low carotenoid period was followed by daily consumption of 330 mL tomato juice, then by 330 mL carrot juice and then by 10 g of spinach powder, each for 2 wk. Antioxidant status [water-soluble antioxidants in serum, ferric reducing ability of plasma (FRAP) and antioxidant enzyme activities] and lipid peroxidation (plasma malondialdehyde and ex vivo oxidation of LDL) were determined. In a subgroup of 10 men, lipoprotein carotenoids were measured. The consumption of carotenoid-rich vegetables significantly increased selected carotenoids in lipoproteins but had only minor effects on their relative distribution pattern. Tomato juice consumption reduced plasma thiobarbituric acid reactive substances (TBARS) by 12% (P: < 0.05) and lipoprotein oxidizability in terms of an increased lag time (18%, P: < 0.05). Carrot juice and spinach powder had no effect on lipid peroxidation. Water-soluble antioxidants, FRAP, glutathione peroxidase and reductase activities did not change during any study period. In evaluating the low carotenoid diet, we conclude that the additional consumption of carotenoid-rich vegetable products enhanced lipoprotein carotenoid concentrations, but only tomato juice reduced LDL oxidation in healthy men.
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PMID:Moderate intervention with carotenoid-rich vegetable products reduces lipid peroxidation in men. 1095 13

Generation of reactive oxygen species by photosensitization is the corner stone of photodynamic therapy of tumors. Cell damage may be mediated by free radical species and lipid peroxidation of their membranes. The effects of oxygen active species (.OH and O(2)(.-) radicals) photogenerated by the novel photosensitizer m-chloroperbenzoic acid (m-CPBA) on human erythrocyte integrity and stability were studied. The biological toxicity of the reactive oxygen species on human red blood cells (RBCs) was evident by increased osmotic fragility, spherocytosis and haemolysis. The haemolysis was increased in concentration and time dependent manner. The lipid peroxidation product thiobarbituric acid reactive substances (TBARS) was elevated in m-CPBA photosensitized RBCs indicating increased oxidative stress. This was accompanied with a depletion of erythrocyte glutathione (GSH). These effects were blunted by hydroxyl radical scavengers, thiourea and mannitol, which might indicate the production of (.)OH radical by photosensitization with m-CPBA. The antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), peroxidase (Px) and glutathione peroxidase (GSH-Px) were elevated in RBCs treated with m-CPBA in the presence and absence of hydroxyl radical scavengers, mannitol and thiourea. These results suggested that the main oxygen radical photogenerated from m-CPBA is O(2)(&z.rad;-) radical, which is transformed to (.)OH radical probably by hydrogen abstraction. This is probably the main damaging oxygen species and played an essential role in oxidative haemolysis mediated by peroxidation of membrane lipids of human erythrocytes. This study provides an investigational promising data for photodynamic therapy.
Cancer Lett 2000 Oct 01
PMID:Photosensitization induced reactive oxygen species and oxidative damage in human erythrocytes. 1096 Jul 65

Four selenocysteine-containing proteins (gastrointestinal glutathione peroxidase, plasma glutathione peroxidase, selenoprotein P, and thioredoxin reductase-alpha) are expressed in the colonic mucosa. Because of their antioxidant functions, a protective role in colon carcinogenesis is discussed. The aim of this study was to elucidate an involvement of gastrointestinal selenoproteins during the adenoma-carcinoma sequence. Matched pairs of biopsies of colorectal adenomas and adjacent normal mucosa from 11 patients were analyzed for mRNA expression, protein expression, or enzyme activity of selenoproteins by Northern blot, Western blot, or enzymatic tests. All adenomas revealed a marked reduction of selenoprotein P and a variable increase of gastrointestinal glutathione peroxidase mRNA compared with adjacent tissue. Thioredoxin reductase-alpha and plasma glutathione peroxidase mRNA expression were not altered in adenomas. The Northern blot results were confirmed by Western blot analysis or enzyme activity measurement, respectively. We conclude that gastrointestinal glutathione peroxidase and selenoprotein P play a complementary role in the antioxidative cell defense along the adenoma-carcinoma sequence. It remains to be shown whether upregulation of gastrointestinal glutathione peroxidase in adenomas represents a compensatory mechanism to reduce susceptibility for oxidative damage resulting from the loss of selenoprotein P.
Nutr Cancer 2000
PMID:Inverse mRNA expression of the selenocysteine-containing proteins GI-GPx and SeP in colorectal adenomas compared with adjacent normal mucosa. 1096 27

Loss of function of the tumor suppressor protein p53 represents a very frequent event in human carcinogenesis, but the molecular mechanisms linking impaired p53 activity to increased cell malignancy are still incompletely understood. p53 is normally involved in both cell cycle control and the induction of cell death and is involved in the latter mainly through the transcriptional regulation of pro- and antiapoptotic proteins. Reactive oxygen species are known to be powerful inducers of p53 activity; moreover, they play a role in the execution of p53-dependent apoptosis. Here we show that transformed mouse fibroblasts lacking p53 are significantly more resistant than wild-type (wt) controls to the cytotoxic effect of a number of pro-oxidant treatments. Interestingly, these cells also exhibit deregulated expression of the antioxidant enzyme manganese superoxide dismutase (MnSOD), a protein known to protect cancer cells from the oxidative injury inflicted by antitumoral cytokines and anticancer drugs. MnSOD activity was also increased in liver tissue from p53-deficient mice in comparison with wt tissue. Transient transfection of wt p53 in HeLa cells led to a significant reduction in steady-state MnSOD mRNA levels and enzymatic activity, confirming that the expression of this antioxidant enzyme is negatively regulated by p53. Forced expression of MnSOD rendered HeLa cells resistant to p53-dependent cytotoxic treatments and, in cotransfection experiments, counteracted the growth-inhibitory effect of p53. Taken together, these data identify MnSOD as a potential target for tumor suppressor protein p53 and underscore the relevance of MnSOD modulation in the context of normal p53 functions because it is consistent with many reports of abnormally increased MnSOD expression in human cancers.
Cancer Res 2000 Aug 15
PMID:Deregulated manganese superoxide dismutase expression and resistance to oxidative injury in p53-deficient cells. 1096 20

The antioxidants and lipid peroxidation products are being extensively studied because of their potential importance and pathogenetic role in several non-communicable diseases like cardiovascular diseases and cancer, but the data on hypertension is scanty. Therefore, the present study aimed to assess the levels of lipid peroxidation and antioxidants besides dislipidemia changes among 32 newly diagnosed male hypertensives by comparing them with an equal sample of normotensives. Significant increase in serum lipid peroxide levels and decrease in antioxidant enzyme superoxide dismutase and vitamins E and A were observed among hypertensives than the controls. Hypertensives had higher total cholesterol, low-density lipoprotein cholesterol, triglycerides, body mass index and low high-density lipoprotein cholesterol levels than normotensives. The percentage prevalence of hypercholesterolemia, hypertriglyceridemia, low high-density lipoprotein cholesterol and obesity was higher in study subjects. Obese hypertensives had significantly higher levels of lipid peroxides and lipids with no change in antioxidant status than normal-weight hypertensives. Our results suggest that hypertensive patients may have elevated lipid peroxidation, lipids and reduced protection from antioxidants, which may contribute to the propensity in such patients to develop cardiovascular diseases, and to correct this, antioxidant supplementation besides weight reduction may be helpful to reduce the severity of burden.
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PMID:Antioxidants, lipid peroxidation and lipoproteins in primary hypertension. 1097 48

Lipid peroxide levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione transferase (GST) activities were investigated in mitochondrial fractions obtained from tumorous and nontumorous colorectal tissues of fourteen patients with colon and rectum cancer. Histopathological evaluations, including type, stage, necrosis and lymphocyte infiltration were also performed for each patient. The activities of SOD, GSH-Px and GST were increased significantly, but lipid peroxide levels remained unchanged in mitochondria obtained from tumors compared to adjacent normal tissues of subjects with colorectal cancer. When the patients were grouped according to their histopathological evaluation, such as type, stage, necrosis and lymphocyte infiltration, no relationship was observed between the histopathological results and the mitochondrial lipid peroxidation or antioxidant enzyme activities.
Jpn J Cancer Res 2000 Dec
PMID:Mitochondrial lipid peroxides and antioxidant enzymes in colorectal adenocarcinoma tissues. 1112 24


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