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)

Prostaglandins (PGs) originate from the degradation of membranar arachidonic acid by cyclooxygenases (COX-1 and COX-2). The prostaglandin actions in the nervous system are multiple and have been suggested to play a significant role in neurodegenerative disorders. Some PGs have been reported to be toxic and, interestingly, the cyclopentenone PGs have been reported to be cytoprotective at low concentration and could play a significant role in neuronal plasticity. They have been shown to be protective against oxidative stress injury; however, the cellular mechanisms of protection afforded by these PGs are still unclear. It is postulated that the cascade leading to neuronal cell death in acute and chronic neurodegenerative conditions, such as cerebral ischemia and Alzheimer's disease, would be mediated by free radical damage. We tested the hypothesis that the neuroprotective action of cyclopentanone could be caused partially by an induction of heme oxygenase 1 (HO-1). We and others have previously reported that modulation of HO total activity may well have direct physiological implications in stroke and in Alzheimer's disease. HO acts as an antioxidant enzyme by degrading heme into iron, carbon monoxide, and biliverdin that is rapidly converted into bilirubin. Using mouse primary neuronal cultures, we demonstrated that PGs of the J series induce HO-1 in a dose-dependent manner (0, 0.5, 5, 10, 20, and 50 micro g/ml) and that PGJ(2) and dPGJ(2) were more potent than PGA(2), dPGA(2), PGD(2), and PGE(2). No significant effects were observed for HO-2 and actin expression. In regard to HO-3 expression found in rat, with its protein deducted sequence highly homologous to HO-2, no detection was observed in HO-2(-/-) mice, suggesting that HO-3 protein would not be present in mouse brain. We are proposing that several of the protective effects of PGJ(2) could be mediated through beneficial actions of heme degradation and its metabolites. The design of new mimetics based on the cyclopentenone structure could be very useful as neuroprotective agents and be tested in animal models of stroke and Alzheimer's disease.
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PMID:Regulation of heme oxygenase expression by cyclopentenone prostaglandins. 1270 76

Copper chaperones are copper-binding proteins that directly insert copper into specific targets, preventing the accumulation of free copper ions that can be toxic to the cell. Despite considerable advances in the understanding of copper transfer from copper chaperones to their target, to date, there is no information regarding how the activity of these proteins is regulated in higher eukaryotes. The insertion of copper into the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) depends on the copper chaperone for SOD1 (CCS). We have recently reported that CCS protein is increased in tissues of rats fed copper-deficient diets suggesting that copper may regulate CCS expression. Here we show that whereas copper deficiency increased CCS protein in rats, mRNA level was unaffected. Rodent and human cell lines cultured in the presence of the specific copper chelator 2,3,2-tetraamine displayed a dose-dependent increase in CCS protein that could be reversed with the addition of copper but not iron or zinc to the cells. Switching cells from copper-deficient to copper-rich medium promoted the rapid degradation of CCS, which could be blocked by the proteosome inhibitors MG132 and lactacystin but not a cysteine protease inhibitor or inhibitors of the lysosomal degradation pathway. In addition, CCS degradation was slower in copper-deficient cells than in cells cultured in copper-rich medium. Together, these data show that copper regulates CCS expression by modulating its degradation by the 26 S proteosome and suggest a novel role for CCS in prioritizing the utilization of copper when it is scarce.
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PMID:Copper modulates the degradation of copper chaperone for Cu,Zn superoxide dismutase by the 26 S proteosome. 1283 19

To characterize the role of intestinal epithelial cells in mucosal host defense, we have examined endogenous antioxidant reactivity and inflammatory response in Caco-2 cell line. When differentiated Caco-2 cells were incubated with iron/ascorbate for 1-24 h, they exhibited increased malondialdehyde levels and decreased polyunsaturated fatty acid proportion in favor of saturated fatty acids. These modifications were accompanied with alterations in membrane fluidity and permeability. The oxidative stress did not induce changes in the antioxidant enzyme activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione transferase, or in cellular glutathione content. However, iron/ascorbate-mediated lipid peroxidation promoted inhibitor-kappaB degradation and NF-kappaB activation, as well as gave rise to IL-8, cyclooxygenase-2, and ICAM-1. These results support the importance of oxidant/antioxidant balance in the epithelial cell inflammatory response.
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PMID:Inflammatory reaction without endogenous antioxidant response in Caco-2 cells exposed to iron/ascorbate-mediated lipid peroxidation. 1284 21

CYP2E1 induction by ethanol is one mechanism by which ethanol creates oxidative stress in the liver. The superoxide dismutases (SODs) are an important antioxidant enzyme defense system against reactive oxygen species (ROS). To investigate the protective role of SOD against CYP2E1-dependent toxicity, a transfected HepG2 cell line overexpressing CYP2E1 (E47 cells) was infected with adenoviral vectors containing Cu/Zn-SOD complementary DNA (cDNA) (Ad.SOD1) and Mn-SOD cDNA (Ad.SOD2). Forty-eight hours after infection, intracellular levels and activity of Cu/Zn-SOD and Mn-SOD were increased about 2- and 3-fold, respectively. Localization of the overexpressed Cu/Zn-SOD in the cytosol and Mn-SOD in the mitochondria was confirmed by assaying the levels and activity of SOD in the corresponding isolated fractions. Arachidonic acid (AA) plus iron-induced cell death was partially prevented in both Ad.SOD1- and Ad.SOD2-infected E47 cells. Overexpression of Cu/Zn-SOD and Mn-SOD also partially protected E47 cells from the increase in reactive oxygen production and lipid peroxidation and the loss of mitochondrial membrane potential induced by AA and iron. Infection with Cu/Zn-SOD and Mn-SOD also protected the E47 cells against AA toxicity or buthionine sulfoximine (BSO)-dependent toxicity. CYP2E1 levels and catalytic activity were not altered by overexpression of Cu/Zn-SOD or Mn-SOD. Cu/Zn-SOD in the cytosol and Mn-SOD in mitochondria each are capable of protecting HepG2 cells expressing CYP2E1 against cytotoxicity induced by pro-oxidants. In conclusion, these enzymes may be useful in the prevention or improvement of liver injury produced by agents known to be metabolized by CYP2E1 to reactive intermediates and to cause oxidative stress.
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PMID:Adenovirus-mediated expression of Cu/Zn- or Mn-superoxide dismutase protects against CYP2E1-dependent toxicity. 1457 53

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

The objective of this study was to assess the oxidative stability and presence of antibiotic residues in tissues of broilers fed diets supplemented with alpha-tocopheryl acetate and treated with enrofloxacin. The activities of antioxidant enzymes and antibiotic concentrations in chicken breast, leg, and liver were determined. Iron-induced TBA-reactive substances (TBARS) and vitamin E were evaluated in muscles. The antioxidant effectiveness of vitamin E was reflected by TBARS values being lower in antioxidant-supplemented treatments than in the other dietary groups. On the other hand, antioxidant enzyme activities were not substantially affected by dietary treatments. The concentration of enrofloxacin in tissues was considerable, even after withdrawal 12 d before slaughter. Contrary to the findings in previous studies, enrofloxacin was not extensively metabolized to ciprofloxacin. Supplementation of the diet with 100 mg/kg of alpha-tocopheryl acetate did not have a significant effect on the level of antibiotic found in breast muscle samples. When comparing treatments without antibiotic withdrawal time, alpha-tocopheryl acetate supplementation led to a significant decrease in enrofloxacin level in leg and liver samples. These results showed that mutual interactions between different molecules could modify the drug residues in the tissue, which should be taken into account when considering the drug administration and the establishment of a correct withdrawal time.
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PMID:Influence of enrofloxacin administration and alpha-tocopheryl acetate supplemented diets on oxidative stability of broiler tissues. 1514 38

The major purpose of this study was to compare the oxidant-related toxicities of the different oral iron preparations in children with iron deficiency anemia (IDA); the second aim was to investigate the side effects of iron preparations. Seventy-two children with IDA were randomly included in the Fe(2+) group (n = 39) or the Fe(3+) group (n = 33). Some oxidizable substrates (erythrocytes malondialdehyde (MDA), urine 8-isoprostane, and basal and Cu-stimulated-oxidized LDL and antioxidant enzyme (superoxide dismutase (SOD), catalase and glutathione peroxidase) activities were evaluated at the beginning and at the 1st, 3rd, and 6th months of therapy. Side effects due to medication were recorded. While at the end of the 1st month SOD levels were significantly increased in Fe(3+) group, at the 6th month evaluation, basal-oxidized LDL levels were significantly increased in the Fe(3+) group, as was urine 8-isoprostane in the Fe(2+) group. No other difference was found between two groups. In conclusion, there were minimal differences between children treated with ferric or ferrous iron in antioxidant system activities, the status of oxidizable substrates, and clinical toxicities.
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PMID:Safety profiles of Fe2+ and Fe3+ oral preparations in the treatment of iron deficiency anemia in children. 1616 57

Recently, intense interest has focused on the antioxidant properties of natural products. In particular, Chinese herbal medicines (CHM) have become hot topics for life science researchers since many are reported to possess cardioprotective compounds, many of which remain to be identified. Indeed, the exact mechanisms by which CHM work remain unknown. Although many of these herbal remedies are undoubtedly efficacious, few have been scientifically investigated for their active chemical constituents and biological activities. We have previously reported higher activities of antioxidant defence enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferases in the liver of rats treated with the herb Salvia miltiorrhiza in a model of acute myocardial infarction. Using well established in vitro antioxidant assays employing 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and diphenyl-l-picrylhydrazyl (DPPH) we have shown that in addition to elevating endogenous antioxidant enzyme activity, Salvia miltiorrhiza and other CHM traditionally used for cardiovascular disorders (such as Rhizoma ligustici, Herba leonuri, Radix achyranthis bidentatae, and Camellia sinensis) contain potent antioxidant moieties in addition to their phenolic constituents. Furthermore, these novel non-phenolic components are effective inhibitors of oxidative reactions mediated by the inflammatory oxidants, peroxynitrite,hypochlorous acid and hydroxyl radical as well as iron-dependent lipid peroxidation. In this review, we discuss the various antioxidant properties of CHM in the context of their biochemical mechanisms.
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PMID:Antioxidants in Chinese herbal medicines: a biochemical perspective. 1528 31

Different members of tricyclic antidepressants (TCAs) were found to induce free radical and oxidative stress in vitro. Accordingly, in the present study we tried to explore the possible role of oxidative stress in TCAs-induced cardiotoxicity. Rats were given a single injection of clomipramine (45 mg/kg). The cardiotoxicity was assessed by measuring ECG parameters (heart rate and QRS widening) and serum lactate dehydrogenase activity. The oxidative stress was assessed by measuring the myocardial reduced glutathione and lipid peroxides levels as well as different antioxidant enzyme activities after 24h of drug injection. In addition, we specifically investigated whether clomipramine could induce hydroxyl radical generation in vitro. The study revealed that clomipramine-induced a significant increase in lipid peroxides level (133%) and a significant decrease in glutathione level (84%) as well as a significant decrease in the activity of glutathione peroxidase and superoxide dismutase by 64% and 73%, respectively, as compared with the control group. In addition, clomipramine at concentrations 10 microM, 25 microM, 50 microM and 100 microM increased hydroxyl radical generation by 148%, 204%, 268% and 391%, respectively. Addition of hydroxyl radical scavenger or iron chelator significantly counteracted the effect of clomipramine. In conclusion, the present study demonstrates that free radical generation and oxidative stress play a role in clomipramine-induced cardiotoxicity. In addition, clomipramine can induce hydroxyl radical in vitro.
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PMID:Does oxidative stress contribute in tricyclic antidepressants-induced cardiotoxicity? 1530 97

Reviews on the pathogenic mechanisms of Shigella species show a lacunae in the understanding of the bacterial antioxidant defense system and its regulations. This study was done to investigate the regulation of expression of antioxidant enzymes in clinical isolates of Shigella species, under various growth conditions. The in vitro expression of superoxide dismutase in the clinical isolates of Shigella spp., is modulated by both endogenous and exogenous factors. During aerobic and iron repleted growth conditions, the expression of the MnSOD and FeSOD enzymes were higher, and an atypical SOD was also expressed. However, under anaerobic growth conditions and in plasmid-cured strains, the antioxidant enzyme activities were decreased and the atypical SOD was not expressed. Absence of the atypical form of SOD may be due to the low oxygen environment. Plasmid-encoded factors may also play a role in the expression of this SOD, which had a molecular weight of approximately 30 kDa. In the rat ileal loop ligation assay, mild lesions were observed only in the intestinal microvilli of rats injected with plasmid-cured strains of Shigella spp., suggesting that plasmid-encoded factors, including those that regulate the expression of the atypical SOD, are essential for the virulence of Shigella spp.
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PMID:Identification of an atypical form of 30 kDa SOD--a possible virulence factor in clinical isolates of Shigella spp. 1566 90


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