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)

I-compounds are bulky indigenous DNA adducts that can be detected by (32)P-postlabeling. A subgroup, termed type II I-compounds, represents DNA lesions induced by oxidative stress. Several major type II I-compounds have been identified as dinucleotides containing 3'-terminal 8,5'-cyclo-2'-deoxyadenosine (cA). Levels of type II I-compounds depend on the pro-oxidant status of the cell. For example, enhanced formation of such oxidative DNA lesions in newborn rodents appears to be a consequence of incomplete development of neonatal antioxidant defense systems. We tested the hypothesis that young mice deficient in NAD(P)H:quinone oxidoreductase 1 (NQO1), an antioxidant enzyme catalyzing the detoxification of quinones and their derivatives, show increased formation of these oxidative DNA lesions. Type II I-compound levels were determined by (32)P-postlabeling in liver and kidney DNA of untreated male wild-type or NQO1-null C57BL/6 mice of different ages. NQO1 catalytic activities and contents were measured by spectrophotometric and Western blotting techniques, respectively. Elevated oxidative adduct levels including those containing cA were detected in NQO1-null compared to wild-type mice at 10, 30 and 90 days in liver and at 30 and 90 days in kidney DNA. Furthermore, there were statistically significant inverse relationships between type II I-compound levels and NQO1 activities in wild-type mice up to 30 days of age. Taken together, the results suggest that NQO1 plays an important role in attenuating endogenous oxidative DNA damage in vivo. Our results show also that type II I-compounds represent useful and sensitive biomarkers with utility in studies of oxidative DNA damage and its consequences.
Int J Cancer 2004 Dec 10
PMID:Effects of NQO1 deficiency on levels of cyclopurines and other oxidative DNA lesions in liver and kidney of young mice. 1538 90

In recent years, the role of selenium in the prevention of a number of degenerative conditions including cancer, inflammatory diseases, thyroid function, cardiovascular disease, neurological diseases, aging, infertility, and infections, has been established by laboratory experiments, clinical trials, and epidemiological data. Most of the effects in these conditions are related to the function of selenium in antioxidant enzyme systems. Replenishing selenium in deficiency conditions appears to have immune-stimulating effects, particularly in patients undergoing chemotherapy. However, increasing the levels of selenoprotein antioxidant enzymes (glutathione peroxidase, thioredoxin reductase, etc.) appears to be only one of many ways in which selenium-based metabolites contribute to normal cellular growth and function. Animal data, epidemiological data, and intervention trials have shown a clear role for selenium compounds in both prevention of specific cancers and antitumorigenic effects in post-initiation phases of cancer.
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PMID:Selenium biochemistry and cancer: a review of the literature. 1538 17

Cancer patients can be divided into 3 groups: those receiving standard or experimental therapy, those who have become unresponsive to these therapies, and those in remission at risk for recurrence or a second new cancer. While impressive progress in standard cancer therapy has been made, the value of this therapy in the management of solid tumors may have reached a plateau. At present, there is no strategy to reduce the risk of recurrence of the primary tumors or of a second cancer among survivors. Patients unresponsive to standard or experimental therapies have little option except for poor quality of life for the remainder of life. Therefore, additional approaches should be developed to improve the efficacy of current management of cancer. In this review, the author proposes that an active nutritional protocol that includes high doses of multiple dietary antioxidants and their derivatives (vitamin C, alpha-tocopheryl succinate, and natural beta-carotene), but not endogenously made antioxidants (glutathione- and antioxidant enzyme-elevating agents), when administered as an adjunct to radiation therapy, chemotherapy, or experimental therapy, may improve its efficacy by increasing tumor response and decreasing toxicity. This nutritional protocol can also be used when patients become unresponsive to standard therapy or experimental therapy to improve quality of life and possibly increase the survival time. The authors also propose that after completion of standard therapy and/or experimental therapy, a maintenance nutritional protocol that contains lower doses of antioxidants and their derivatives, together with modification in diet and lifestyle, may reduce the risk of recurrence of the original tumor and development of a second cancer among survivors. Experimental data and limited human studies suggest that use of these nutritional approaches may improve oncologic outcomes and decrease toxicity. This review also discusses the reasons for the current debates regarding the use of antioxidants during radiation or chemotherapy.
Integr Cancer Ther 2004 Dec
PMID:Multiple dietary antioxidants enhance the efficacy of standard and experimental cancer therapies and decrease their toxicity. 1552 2

Glutathione peroxidase is a selenium-containing, antioxidant enzyme previously implicated in the risk and development of lung and breast cancer, in part the result of allelic loss at the GPx-1 locus. This study examined allelic loss at the same locus in squamous cell carcinomas of the head and neck. The frequency of a polymorphism at codon 198 resulting in either a leucine or a proline at that position was surveyed by comparing 133 DNA samples obtained from head and neck tumors and 517 samples obtained from cancer-free individuals. Tumor DNAs exhibited fewer pro/leu heterozygotes as compared to DNA obtained from the cancer-free population. Fewer GPx-1 heterozygotes were verified by determining the frequency of highly polymorphic alanine repeat sequences in the same gene. The analysis revealed an approximately 42% reduction in heterozygosity in the DNA from the tumor samples. In order to assess loss of heterozygosity (LOH) at the GPx-1 locus, DNA was genotyped from peripheral lymphocytes, tumor tissue, and microscopically normal tissues adjacent to the tumor, derived from the same patients. These studies indicated LOH at the GPx-1 locus in each of the three tumor/normal tissues sample sets examined. Furthermore, LOH in the microscopically normal tissues at the tumor margin occurred in two of the three sample sets examined. These data implicate GPx-1 in the development of squamous cell carcinoma the head and neck and suggest that allelic loss of this gene, or one tightly linked to it, is an early event in the development of this type of malignancy.
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PMID:Allelic loss at the GPx-1 locus in cancer of the head and neck. 1555 74

Many studies have shown the balance between the oxygen reactive species (ROS) and the antioxidant capacities, and that the massive ROS generation could lead to cell damage and diseases such as atherosclerosis, aging and cancer. Changes in antioxidant capacity like free radicals scavenging antioxidant agents such as vitamin E, C content, serum concentrations of bilirubin, uric acid, albumin and antioxidant enzyme systems like SOD, and GPx activities have been described to be related to many diseases. However, the research on chronic airway inflammatory disease and the antioxidant defence system is still not enough. Understanding of the antioxidant status and antioxidant enzymes in asthmatic patients is still unclear. In the present controlled study, we investigated the total antioxidant status (TAS) in serum and the antioxidant enzyme (total SOD and GPx) activities in 46 asthmatic children and 52 normal controls. The serum level of TAS in asthmatic children was significantly lower than the controls. The SOD concentration in asthmatic children was higher than the control, however the GPx was much lower than the control children, even though it was not statistical significance. In conclusion, these results suggested the existence of higher oxidative stress and reactive oxygen species (ROS) in asthmatic children, and that the antioxidant capacities in asthmatic children were altered. If the production of ROS was persistent, it would result in chronic inflammation and the imbalance of oxidative-reductive status in those patients.
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PMID:Evaluation of the serum antioxidant status in asthmatic children. 1562 67

Thioredoxin reductase (TRX) is a selenoprotein that reduces oxidized protein substrates in an NADPH-dependent process (cf. Fig. 1). The thioredoxins (TX) are a family of small redox active proteins that undergo reversible oxidation/reduction and help to maintain the redox state of cells. TX serves as a cofactor in many TRX-catalyzed reductions in a manner similar to glutathione (GSH) in thioltransferase reactions. For example, TX is a cofactor in protein disulfide reduction and DNA synthesis, but independently, it inhibits apoptosis, stimulates cell proliferation and angiogenesis, and increases transcription factor activity. The role of the TRX/TX system is limited by its reducing capacity as well as the additional supply of electrons in the form of NADPH provided by hexose monophosphate shunt (HMPS). TX is limited by the reduction capacity of its vicinal sulfhydryls and needs a source of electrons from the HMPS and TRX- coupled system to reduce disulfides. Oxidized TX is reduced by TRX and NADPH. Several lines of evidence suggest that the coupled HMPS/TRX/TX system represents an important target for cancer therapy. TX overexpression has been reported in several malignancies and may be associated with aggressive tumor growth and poor survival. In some cells, TX is an important factor in conferring resistance to chemotherapy and in stimulating production of hypoxia-inducible factor (HIF-1). Several inhibitors of the TRX/TX system have been evaluated in experimental cancer models: these include HMPS inhibitors, carbohydrate analogues, NADP synthesis blockers, vicinal thiol reactants, cisplatin, and TRX inhibitors. More recently, the targeted anti-cancer agent motexafin gadolinium has been identified. Motexafin gadolinium is a redox mediator that selectively localizes to cancer cells, and reacts with reducing metabolites and vicinal thiols to generate reactive oxygen species that ultimately block the TRX enzyme as well as the analogous glutaredoxin activity. In cell and animal models, motexafin gadolinium is directly cytotoxic to various tumor cells and enhances the activity of radiation therapy and chemotherapy. This drug is now in a broad range of clinical trials investigating its therapeutic potential when used as a single agent or in combination with either chemotherapy or radiation therapy. Promising clinical activity has been reported in a clinical trial with motexafin gadolinium and whole brain radiation therapy for treatment of brain metastases from solid tumors. These findings suggest that the TRX/TX system may represent an attractive target for development of new cancer therapeutics.
Cancer Biol Ther 2005 Jan
PMID:The thioredoxin reductase/thioredoxin system: novel redox targets for cancer therapy. 1568 6

Chronic inflammation is often associated with increased cancer frequency. Continuous exposure to reactive oxygen species, as at the site of chronic inflammation, can result in cells with increased antioxidant defense enzymes. In WEHI7.2 cells, overexpression of catalase or thioredoxin by transfection or selection of a cell population resistant to hydrogen peroxide has resulted in WEHI7.2 variants with altered glucose and energy metabolism. This metabolic change would favor survival in a tumor environment. We conclude that metabolic alterations, due to increased antioxidant enzyme expression, may underlie the increased tumorigenicity seen previously in the variants and contribute to the increased tumor risk associated with chronic inflammation.
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PMID:Increasing the antioxidant defense in WEHI7.2 cells results in a more tumor-like metabolic profile. 1570 45

Oxidative stress may enhance prostatic carcinogenesis. A polymorphism [valine (V) --> alanine (A)] of manganese superoxide dismutase (MnSOD), the primary antioxidant enzyme in mitochondria, has been recently associated with prostate cancer. We examined the relationship between prostate cancer and the MnSOD polymorphism and its interactions with baseline plasma antioxidant levels (selenium, lycopene, and alpha-tocopherol) and beta-carotene treatment among 567 cases and 764 controls nested in the prospective Physicians' Health Study. We found little overall association between MnSOD polymorphism and prostate cancer risk; however, this polymorphism significantly modified risk of prostate cancer associated with prediagnostic plasma antioxidants (P(interaction) > or = 0.05). Among men with the AA genotype, high selenium level (4th versus 1st quartile) was associated with a relative risk (RR) of 0.3 [95% confidence interval (CI), 0.2-0.7] for total prostate cancer; for clinically aggressive prostate cancer, the RR was 0.2 (95% CI, 0.1-0.5). In contrast, among men with the VV/VA genotype, the RRs were 0.6 (0.4-1.0) and 0.7 (0.4-1.2) for total and clinically aggressive prostate cancer. These patterns were similar for lycopene and alpha-tocopherol and were particularly strong when these antioxidants and selenium were combined; men with the AA genotype had a 10-fold gradient in risk for aggressive prostate cancer across quartiles of antioxidant status. Men with AA genotype who were randomly assigned to beta-carotene treatment (versus placebo) had a RR of 0.6 (95% CI, 0.2-0.9; P(interaction) = 0.03) for fatal prostate cancer, but no significant association was observed in men with the VV/VA genotype. Both endogenous and exogenous antioxidants play an important and interdependent role in preventing clinically significant prostate cancer.
Cancer Res 2005 Mar 15
PMID:Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer. 1578 67

To clarify the mechanism by which radon hot springs prevent cancer or not, in this study, blood was collected from residents in the Misasa hot spring district and in a control district. The level of a representative cancer-suppressive gene, p53, and the activity of a representative antioxidant enzyme, superoxide dismutase (SOD), were analyzed as indices. The level of serum p53 protein in the males in the Misasa hot spring district was found to be 2-fold higher than that in the control district, which is a significant difference. In the females in the Misasa hot spring district, SOD activity was approximately 15% higher than that in the control district, which is also statistically significant, and exceeded the reference range of SOD activity despite advanced age. These results suggested that routine exposure of the residents in the Misasa hot spring district to radon at a concentration about 3 times higher than the national mean induces trace active oxygen in vivo, potentiating products of cancer-suppressive gene and antioxidant function. As the p53 protein level was high in the residents in the Misasa hot spring district, apoptosis of cancer cells may readily occur.
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PMID:The elevation of p53 protein level and SOD activity in the resident blood of the Misasa radon hot spring district. 1580 55

Oxygen free radicals and related reactive species have been implicated in the etiology of many diseases, such as atherosclerosis, neurodegenerative disorders, and cancer. Antioxidant enzymes exist in cells to protect against the effects of these free radicals and other oxygen-derived species, which are produced during the oxidative stress. Tea (Camellia sinensis) is the most commonly consumed beverage worldwide. Both green and black tea are known to possess many pharmacological properties, including antioxidant, antipyretic, antibacterial, and antineoplastic effects. In the present study, the preventive effects of black tea extract (BTE) was evaluated in Swiss albino mice against 7,12-dimethyl benz(a)anthracene (DMBA)-induced oxidative stress. The animals were given 0.5%, 1%, and 1.5% BTE as the sole source of drinking solution for 1 week prior to the administration of DMBA, which was given orally as a single dose of 50 mg/kg body weight. At the end of the study period, the liver, kidney, and prostate tissues were dissected out for the determination of antioxidant enzyme levels (catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase), and lipid peroxidation. A dose-dependent protective effect of BTE against DMBA-induced depletion in enzymes activity was observed in all three tissues examined. Similarly, a significant dose-dependent inhibition of the lipid peroxidation caused by DMBA was observed in the BTE-administered animals in all three tissues examined. Our results revealed that BTE provides protection against oxidative damage induced by xenobiotics.
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PMID:Antioxidant potential of black tea against 7,12-dimethylbenz(a)anthracene- induced oxidative stress in Swiss albino mice. 1583 Oct 83


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