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)

Superoxide radicals are known to inhibit progesterone production by luteal cells and have also been reported to cause apoptosis in various cells. The corpus luteum has an antioxidant enzyme to scavenge superoxide radicals: copper-zinc superoxide dismutase (Cu, Zn-SOD). However, it remains unknown how the decrease in intracellular Cu,Zn-SOD activity influences luteal function. This study was therefore undertaken to investigate whether suppression of intracellular Cu,Zn-SOD activity inhibits progesterone production by rat luteal cells and causes apoptosis. To suppress intracellular Cu, Zn-SOD activity, dispersed rat luteal cells were incubated with Cu, Zn-SOD antisense oligonucleotides. The 48-h treatment with antisense oligonucleotides (10 microM) inhibited Cu,Zn-SOD activity by 50% and Cu,Zn-SOD mRNA level by 30%, whereas sense oligonucleotides used as the control had no effect. Progesterone concentration in the medium was significantly decreased by the 48-h treatment with antisense oligonucleotides in the presence of hCG, and this inhibitory effect was completely blocked by the simultaneous addition of N-acetyl-L-cysteine, an antioxidant. Treatment with antisense oligonucleotides caused no significant change in the percentage of apoptotic cells as morphologically evaluated by the nuclear staining with Hoechst dye. In conclusion, the decrease in intracellular Cu, Zn-SOD activities inhibits progesterone production by rat luteal cells, which may be mediated by superoxide radicals, suggesting that intracellular Cu,Zn-SOD plays important roles in the regulation of luteal function.
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PMID:Suppression of intracellular superoxide dismutase activity by antisense oligonucleotides causes inhibition of progesterone production by rat luteal cells. 1049 54

Heme oxygenase (HO) is believed to be a potent antioxidant enzyme in the nervous system; it degrades heme from heme-containing proteins, giving rise to carbon monoxide, iron, and biliverdin, which is rapidly reduced to bilirubin. The first identified isoform of the enzyme, HO1, is an inducible heat-shock protein expressed in high levels in peripheral organs and barely detectable under normal conditions in the brain, whereas HO2 is constitutive and most highly concentrated in the brain. Interestingly, although HO2 is constitutively expressed, its activity can be modulated by phosphorylation. We demonstrated that bilirubin, formed from HO2, is neuroprotectant, as neurotoxicity is augmented in neuronal cultures from mice with targeted deletion of HO2 (HO2(-/-)) and reversed by low concentrations of bilirubin. We now show that neural damage following middle cerebral artery occlusion (MCAO) and reperfusion, a model of focal ischemia of vascular stroke, is substantially worsened in HO2(-/-) animals. By contrast, stroke damage is not significantly altered in HO1(-/-) mice, despite their greater debility. Neural damage following intracranial injections of N-methyl-d-aspartate (NMDA) is also accentuated in HO2(-/-) animals. These findings establish HO2 as an endogenous neuroprotective system in the brain whose pharmacologic manipulation may have therapeutic relevance.
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PMID:Heme oxygenase-2 is neuroprotective in cerebral ischemia. 1060 74

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.
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PMID:The role of cellular glutathione peroxidase redox regulation in the suppression of tumor cell growth by manganese superoxide dismutase. 1091 71

Exposure to 2,4,6-trinitrotoluene (TNT) has been shown to cause induction of cataract in which oxidative stress plays a critical role. From bovine lens we purified to homogeneity and identified an enzyme that catalyzes the reduction of TNT, resulting in the production of reactive oxygen species. The final preparation of TNT reductase showed a single band with a subunit molecular weight of 38 kDa on SDS-PAGE. Sequence data from peptides obtained by digestion with lysylendopeptidase Achromobacter protease I (API) revealed that TNT reductase is identical to zeta-crystallin. Superoxide anions were formed during reduction of TNT by zeta-crystallin, though negligible enzyme activity or protein content for superoxide dismutase, a superoxide scavenging enzyme, was found in the lens. Thus, the present results suggest that the induction of cataracts by TNT may be associated with increased oxidative stress, as a result of reductive activation of TNT generating superoxide anions, there being minimal antioxidant enzyme activity for defense against reactive oxygen species exogenously produced in the lens.
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PMID:Zeta-crystallin catalyzes the reductive activation of 2,4,6-trinitrotoluene to generate reactive oxygen species: a proposed mechanism for the induction of cataracts. 1093 May 85

Inflammation in the dental pulp is accompanied by release of a wide variety of highly oxidative molecules known as reactive oxygen species (ROS). ROS concentrations are controlled in vivo by an antioxidant enzyme scavenger system that may be overwhelmed by the increases in ROS production seen during inflammation. Supplementation of the antioxidant defense system, therefore, may limit the severity of the inflammatory response to injury due to this component. To test this hypothesis, this study examined the effects of superoxide radical scavenging on pulpal inflammation induced in rat molars by standardized cavity preparation. The extent of pulp inflammation was compared histomorphometrically between animals treated with exogenous administration of a human recombinant antioxidant enzyme, copper-zinc superoxide dismutase, conjugated to polyethylene glycol (hr-CuZn-SOD), versus saline-vehicle controls. There was a statistically significant reduction in area of inflammation involvement in those animals treated with hrCuZn-SOD, compared with controls. Although hrCuZn-SOD administration did not completely eliminate inflammation in all animals treated, there was a statistically significant lessening of the severity of the inflammatory response, as well as a greater degree of reparative dentin observed in the hrCuZn-SOD-treated animals.
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PMID:The anti-inflammatory effects of human recombinant copper-zinc superoxide dismutase on pulp inflammation. 1148 50

Reactive oxygen species have been shown to play important roles in v-Ha-Ras mitogenic signaling. We hypothesized that v-Ha-Ras overexpression would induce superoxide production, and therefore modify expression of the primary antioxidant enzyme system. We have demonstrated that immortal rat kidney epithelial cells stably transduced with constitutively active v-Ha-ras produced significantly larger amounts of superoxide radical than wild-type or vector-transfected control cells. The levels of the primary antioxidant enzymes copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase were increased in the superoxide-overproducing cells. DNA-binding activities of the transcription factors activator protein-1, activator protein-2, and nuclear factor-kappaB were all enhanced in the superoxide-overproducing cells. These v-Ha-ras transduced cells also had a shortened cell doubling time and higher plating efficiency, and displayed greater constitutive levels of phosphorylated mitogen-activated protein kinases. These data demonstrate that v-Ha-Ras overexpression increases superoxide production and this apparently affects a wide variety of cell signaling and redox systems.
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PMID:V-Ha-Ras overexpression induces superoxide production and alters levels of primary antioxidant enzymes. 1155 55

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.
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PMID:Overexpression of copper zinc superoxide dismutase suppresses human glioma cell growth. 1186 5

Cisplatin-induced nephrotoxicity is closely associated with an increase in lipid peroxidation. In several previous reports it was claimed that acetylsalicylic acid (ASA) shows its therapeutic potential as a free radical scavenger. The aim of the study was to investigate effects of ASA on cisplatin induced nephrotoxicity in an experimental rat model. Control animals (n:7) were administered 1 mL saline solution intraperitoneal (i.p.). Cisplatin group (n:7) was treated with a single dose of cisplatin i.p. (6 mg/kg), ASA group (n:7) was treated with i.p. (2.5 mg/kg) per day during the study, cisplatin plus ASA group (n:7) was administered single dose cisplatin i.p. (6 mg/kg) plus ASA (2.5 mg/kg) during 5 days. At the end of the study, Catalase (CAT), Glutathione Peroxidase (GSH-Px), Superoxide Dismutase (SOD), Nitric Oxide Synthase (NOS) enzymes activities and Malondialdehyde (MDA), Antioxidant Potential (AOP) levels were measured in both erythrocytes and renal tissues. Urea and creatinine levels and renal tissue necrosis in cisplatin plus ASA group were significantly lower than cisplatin group (p = 0.000, p = 0.014, p = 0.015). SODr activities and MDAr levels of cisplatin plus ASA group were also significantly lower than cisplatin group (p = 0.000, p = 0.029). These results show that cisplatin and ASA combination decreases the levels of urea and creatinine, reduces necrosis and improves antioxidant enzyme activities, MDA and AOP in rat kidney.
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PMID:The protective effects of acetylsalicylic acid on free radical production in cisplatin induced nephrotoxicity: an experimental rat model. 1458 80

Compelling experimental and epidemiological evidence involves oxygen radicals in carcinogenesis, acting reactive oxygen species both as endogenous genotoxins during cell initiation and as messenger molecules in mitogenesis and in tumor promotion. Moreover, oxidants stimulate neoangiogenesis, which is a prerequisite for tumor growth. However, while several natural as well as synthetic antioxidant compounds appear to be chemopreventive in mutagenicity assays, antioxidant-based treatments for the prevention or cure of cancer have led to non-conclusive if not disappointing results. This is likely due to the fact that oxygen radicals have also a major role in the natural defences against the propagation of cancer cells, i.e. tumor cell apoptosis and immune surveillance, and mediate the beneficial cytotoxic effect of both the chemo-and radio-therapy. In recent years, the mitochondrial antioxidant enzyme, Manganous Superoxide Dismutase (MnSOD), has received a growing attention as a negative modulator of cellular apoptosis and as a survival factor for cancer cells. In fact, while overexpression of this enzyme in cancer cells decreases proliferation and tumor incidence in transgenic models, it is clear that even small amounts of this enzyme are crucial for cell resistance to inflammatory stimuli and anticancer drugs, and prevent oncogene-induced apoptosis triggered by the tumor suppressor protein p53. A previously unexpected oncogenic potential of MnSOD is also suggested by the elevated levels of this enzyme in several classes of human neoplasms, in a fashion which often correlates with the degree of their malignancy. This review focuses on the debated issue of the pro- and/or anti-tumoral effect of MnSOD, with special emphasis on recent observations suggesting that pharmacological inhibition of MnSOD may represent an effective strategy to selectively kill cancer cells and to circumvent their resistance to the commonly used anticancer treatments.
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PMID:Mitochondrial superoxide dismutase: a promising target for new anticancer therapies. 1513 21

Copper, zinc-superoxide dismutase (CuZn-SOD) is a cytosolic, antioxidant enzyme that scavenges potentially damaging superoxide radical (()O(2)(-)). Under the proper conditions, CuZn-SOD also catalyzes the oxidation and reduction of certain small molecules. Here, we demonstrate that increased exposure to hydrogen peroxide (H(2)O(2)), a by-product of the ()O(2)(-) scavenging reaction, dramatically increases the ability of CuZn-SOD to oxidize melatonin and reduce S-nitrosoglutathione (GSNO). After a 15min in vitro incubation with CuZn-SOD and 1mM H(2)O(2), 76% of the melatonin was oxidized, compared to 52% with 0.25mM H(2)O(2), and just 9% without H(2)O(2). Pre-incubation with 1mM H(2)O(2) resulted in a 100% increase in the rate of GSNO breakdown by CuZn-SOD in the presence of glutathione (GSH) compared to untreated CuZn-SOD. Collectively, these data suggest that even small increases in intracellular H(2)O(2) levels may result in the oxidation and/or reduction of small molecules critical for proper cellular function.
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PMID:Accelerated CuZn-SOD-mediated oxidation and reduction in the presence of hydrogen peroxide. 1546 39


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