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)

During both mild and severe ischemia, vascular endothelial cells lining large and small vessels of the ischemic organ are exposed to oxygen-derived free radicals resulting in oxidative damage to the organ. Heat shock has been shown to induce thermotolerance and also protect against ischemic injury, possibly via increased synthesis of heat shock proteins (HSPs). We hypothesized that heat shock preconditioning may protect human endothelial cells against oxidative damage. Cultured human umbilical vein endothelial cells (HUVEC) were subjected to heat shock (42 degrees C, 1 h) and allowed to recover for 2 or 20 h, at which times the cells were oxidatively stressed for 1 h by exposing them to 100-200 mumol/l of hydrogen peroxide (H2O2). Cellular damage was assessed immediately and 18 h later by morphology and release of lactate dehydrogenase (LDH). No protection of HUVEC was seen using the 2-hour recovery interval, but a significant protection (P < 0.05) was observed after the 20-hour delay. Northern blot analysis at 1 and 2 h after heating showed induction of HSP-70 mRNA. Western blot analysis demonstrated a significant increase in HSP-72 protein after 2 as well as 20 h of recovery from heat shock, although the amounts of protein at the two times were not significantly different. Furthermore, no differences in the activity of the antioxidant enzyme catalase were observed between heated and unheated HUVEC at 2 and 20 h after heat preconditioning. Thus, heat shock preconditioning induces delayed protection against oxidative injury in HUVEC, and the mechanism of protection appears to involve more than the expression of HSP-72 or activity of catalase.
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PMID:Heat shock provides delayed protection against oxidative injury in cultured human umbilical vein endothelial cells. 999 May 44

Neutrophils have the capacity to produce free radicals. Free radicals are associated with hyperlipoproteinemia and atherosclerotic processes. For this reason, neutrophil superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), catalase (Cat) activities and thiobarbituric acid reactive substances (TBARS), as an index of lipid peroxidation, have been studied in hyperlipoproteinemic (HLP) and age-matched normolipidemic groups. Lipid parameters including triglycerides, total cholesterol, plasma TBARS, HDL-cholesterol, LDL-cholesterol, apo A-I, apo B have also been determined. Forty subjects (females 18, males 22) with HLP (mean age 43.8+/-8.7 (S.D.)) and 40 normolipoproteinemic subjects (females 17, males 23; mean age 46.4+/-11) were included in the study. Neutrophils were isolated by Percoll gradient centrifugation from venous blood samples. Methods used were as follows: INT method for SOD, UV method at 340 nm based on oxidation of NADPH for GSH-Px and GR, UV method at 240 nm based on degradation of hydrogen peroxide for catalase, and a method based on reaction with thiobarbituric acid for TBARS. Neutrophil SOD, GSH-Px, and catalase activities were found to be significantly low in the hyperlipoproteinemic group compared with the normolipoproteinemic group. GR activity did not differ between both groups. The mean TBARS level in the neutrophil fraction was found to be significantly higher in hyperlipoproteinemics than in that of the normolipoproteinemics. It was concluded that decreased neutrophil antioxidant enzyme activities in hyperlipoproteinemics may lead to insufficient detoxification of free radicals produced in these cells and contribute to increased lipid peroxidation.
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PMID:Decreased neutrophil antioxidative enzyme activities and increased lipid peroxidation in hyperlipoproteinemic human subjects. 1006 27

Glutathione peroxidase (GPX) is a primary antioxidant enzyme that scavenges hydrogen peroxide or organic hydroperoxides. We have recently found that GPX is induced by etoposide, a topoisomerase II inhibitor and a p53 activator. In a search for a cis-element that confers potential p53 regulation of GPX, we identified a p53 binding site in the promoter of the GPX gene. This site bound to purified p53 as well as p53 in nuclear extract activated by etoposide. A luciferase reporter driven by a 262-base pair GPX promoter fragment was transcriptionally activated by wild type p53 in a p53 binding site-dependent manner. The same reporter was also activated in a p53 binding site-independent manner by several p53 mutants. The p53 binding and transactivation of the GPX promoter were enhanced by etoposide in p53-positive U2-OS cells. Etoposide-induced transactivation was blocked by a dominant negative p53 mutant, indicating that endogenous wild type p53, upon activation by etoposide, transactivated the GPX promoter. Furthermore, expression of endogenous GPX was induced significantly at both mRNA and enzyme activity levels by etoposide in U2-OS cells but not in p53-negative Saos-2 cells. This is the first report demonstrating that GPX is a novel p53 target gene. The finding links the p53 tumor suppressor to an antioxidant enzyme and will facilitate study of the p53 signaling pathway and antioxidant enzyme regulation.
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PMID:Transcriptional activation of the human glutathione peroxidase promoter by p53. 1020 30

This paper reviews what is currently known about the redox state of the glutamate synapse and its possible role in modulating synaptic plasticity and thus learning and neurocomputation. The hypothesis is presented that the growth or pruning of the synaptic spine is controlled in part by the balance in the synapse between neurodestructive pro-oxidants (e.g., nitric acid radical and hydrogen peroxide) and neuroprotective antioxidants (e.g., ascorbate and carnosine). In addition, there may be a role for catecholamines, in particular dopamine, related to its role in reinforcement signalling. Activation of the dopamine D2 receptor induces the synthesis of an antioxidant enzyme, possibly catalase. Dopamine may also affect the redox balance in the glutamate synapse directly by diffusion from the adjacent dopaminergic bouton-en-passage. Catecholamines are powerful antioxidants, scavengers of free radicals and iron chelators. Catecholamine-iron complexes are potent dismuters of superoxide ions. Additional agents participating in spine pruning may be neurotoxic catecholamine o-quinones present in the brain. This system may be at fault in schizophrenia and Parkinson's disease. Experiments to test the hypothesis are suggested.
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PMID:Redox mechanisms at the glutamate synapse and their significance: a review. 1032 73

It was studied the relation between activities of ferments an antioxidant system: of superoxide dismutase, catalase and GSH-peroxidase in the homogenates of livers, lungs and cerebrum of intact rats. When activities were brought to identical units of measurement, it was determined that relation of activities can see with a point to view of chemical kinetics laws for consecutively-parallel reactions. It is followed from the result that the activity of catalase livers can be explained by the participation of catalases in other reactions, which were connected with forming a hydrogen peroxide. From the relations between ferments of antioxidant system it was discovered that GSH-peroxidase is the most important antioxidant enzyme for the cerebrum. Data of the relation of activities ferments of antioxidant system are stipulated by the tissues particularities and they are reflected a contribution of every biocatalyst in that system.
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PMID:[Relationship between values of antioxidant enzyme system activity in various tissues of intact rats]. 1040 49

Cytochrome c peroxidase oxidises hydrogen peroxide using cytochrome c as the electron donor. This enzyme is found in yeast and bacteria and has been also described in the trematodes Fasciola hepatica and Schistosoma mansoni. Using partially purified cytochrome c peroxidase samples from Fasciola hepatica we evaluated its role as an antioxidant enzyme via the investigation of its ability to protect against oxidative damage to deoxyribose in vitro. A system containing FeIII-EDTA plus ascorbate was used to generate reactive oxygen species superoxide radical, H2O2 as well as the hydroxyl radical. Fasciola hepatica cytochrome c peroxidase effectively protected deoxyribose against oxidative damage in the presence of its substrate cytochrome c. This protection was proportional to the amount of enzyme added and occurred only in the presence of cytochrome c. Due to the low specific activity of the final partially purified sample the effects of ascorbate and calcium chloride on cytochrome c peroxidase were investigated. The activity of the partially purified enzyme was found to increase between 10 and 37% upon reduction with ascorbate. However, incubation of the partially purified enzyme with 1 mM calcium chloride did not have any effect on enzyme activity. Our results showed that Fasciola hepatica CcP can protect deoxyribose from oxidative damage in vitro by blocking the formation of the highly toxic hydroxyl radical (.OH). We suggest that the capacity of CcP to inhibit .OH-formation, by efficiently removing H2O2 from the in vitro oxidative system, may extend the biological role of CcP in response to oxidative stress in Fasciola hepatica.
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PMID:Characterisation of Fasciola hepatica cytochrome c peroxidase as an enzyme with potential antioxidant activity in vitro. 1040 59

Reactive oxygen species (ROS) are important second messengers for the induction of several genes in a variety of physiological and pathological conditions. Here we addressed the question of whether isolated, unbalanced overexpression of the antioxidant enzyme manganese superoxide dismutase (Mn-SOD) may modulate signal transduction cascades, finally leading to connective tissue degradation, a hallmark in carcinogenesis and aging. Therefore, we generated stably Mn-SOD-overexpressing fibroblasts with an up to 4. 6-fold increase in Mn-SOD activity. The Mn-SOD-overexpressing cells revealed specific resistance to the superoxide anion (O-(2))-generating agent paraquat, whereas no resistance to UVA-generated oxidative stress was found. Treatment of the Mn-SOD-overexpressing cells with various ROS-generating systems resulted (due to the enhanced dismutation of superoxide anion to hydrogen peroxide) in an up to 9.5-fold increase in matrix-degrading metalloprotease-1 (MMP-1) mRNA levels. A similar increase in MMP-1 mRNA was also seen when the intracellular H(2)O(2) concentration was increased by the inhibition of different H(2)O(2)-detoxifying pathways. Furthermore, prooxidant conditions led to a strong induction of c-jun and c-fos mRNA levels resulting in a 4-fold higher transactivation of the transcription factor AP-1 in the Mn-SOD-overexpressing cells. Collectively, we have found that enhanced Mn-SOD activity, via an unbalanced H(2)O(2) overproduction and detoxification, induces MMP-1 mRNA levels, and this effect is at least partly mediated by the DNA recognition sequence AP-1.
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PMID:Stable overexpression of manganese superoxide dismutase in mitochondria identifies hydrogen peroxide as a major oxidant in the AP-1-mediated induction of matrix-degrading metalloprotease-1. 1046 29

Dominant mutations in the copper/zinc superoxide dismutase (SOD1) gene have been observed in 15-20% of familial amyotrophic lateral sclerosis (FALS) cases. The mechanism by which SOD1 mutations result in motor neuron degeneration in FALS mice partly involves oxidative damage and an increased peroxidase activity of the mutant SOD1. A new therapeutic approach designed to eliminate the substrate of this peroxidase activity was examined in two lines of transgenic mice expressing the FALS-linked mutation glycine to alanine (G93A). We investigated the ability of putrescine-modified catalase (PUT-CAT), an antioxidant enzyme that removes hydrogen peroxide and has increased permeability at the blood-brain barrier, to modify the time course of the SOD1 mutation-induced motor neuron disease in these FALS mice. Continuous, subcutaneous administration of PUT-CAT significantly delayed the age at which onset of clinical disease occurred (indicated by loss of splay and/or tremors of hindlimbs) in a high-expressor line of FALS transgenic mice. Intraperitoneal injection of PUT-CAT given two times per week also significantly delayed the onset of clinical disease in a low-expressor line of FALS mice. PUT-CAT also significantly delayed the age at which clinical weakness developed (quantified by measuring the shortening of stride length) in both lines of FALS animals. No significant changes were observed in the survival times of the high-expressor FALS mice in any of the treatment groups. However, a trend toward a prolongation of survival was observed in the PUT-CAT-treated low-expressor FALS mice. These results support the role of free radical-mediated damage in the cascade of events leading to motor neurodegeneration in FALS and indicate that PUT-CAT interacts with a critical step in this cascade to delay the onset of clinical disease as well as the development of clinical weakness in FALS transgenic mice.
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PMID:Therapeutic benefits of putrescine-modified catalase in a transgenic mouse model of familial amyotrophic lateral sclerosis. 1048 88

We have isolated the cDNAs encoding human and mouse homologues of a yeast protein, termed peroxisomal membrane protein 20 (PMP20). Comparison of the amino acid sequences of human (HsPMP20) and mouse (MmPMP20) PMP20 proteins revealed a high degree of identity (93%), whereas resemblance to the yeast Candida boidinii PMP20A and PMP20B (CbPMP20A and CbPMP20B) was less (30% identity). Both HsPMP20 and MmPMP20 lack transmembrane regions, as do CbPMP20A and CbPMP20B. HsPMP20 mRNA expression was low in human fetal tissues, especially in the brain. In adult tissues, HsPMP20 mRNA was expressed in the majority of tissues tested. HsPMP20 and MmPMP20 contained the C-terminal tripeptide sequence Ser-Gln-Leu (SQL), which is similar to the peroxisomal targeting signal 1 utilized for protein import into peroxisomes. HsPMP20 bound directly to the human peroxisomal targeting signal 1 receptor, HsPEX5. Mutagenesis analysis showed that the C-terminal tripeptide sequence, SQL, of HsPMP20 is necessary for its binding to HsPEX5. Subcellular fractionation of HeLa cells, expressing epitope-tagged PMP20, revealed that HsPMP20 is localized in the cytoplasm and in a particulate fraction containing peroxisomes. Double-staining immunofluorescence studies showed colocalization of HsPMP20 and thiolase, a bona fide peroxisomal protein. The amino acid sequence alignment of HsPMP20, MmPMP20, CbPMP20A, and CbPMP20B displayed high similarity to thiol-specific antioxidant proteins. HsPMP20 exerted an inhibitory effect on the inactivation of glutamine synthetase in the thiol metal-catalyzed oxidation system but not in the nonthiol metal-catalyzed oxidation system, suggesting that HsPMP20 possesses thiol-specific antioxidant activity. In addition, HsPMP20 removed hydrogen peroxide by its thiol-peroxidase activity. These results indicate that HsPMP20 is imported into the peroxisomal matrix via PEX5p and may work to protect peroxisomal proteins against oxidative stress. Because some portion of PMP20 might also be present in the cytosol, HsPMP20 may also have a protective effect in the cytoplasm.
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PMID:Characterization of human and murine PMP20 peroxisomal proteins that exhibit antioxidant activity in vitro. 1051 71

Reactive oxygen species (ROS) comprise several oxygen containing compounds, among them hydrogen peroxide (H2O2), which are generated by internal and external sources and play pleiotropic roles in physiological and pathological states. Skin cells as well as cells from other tissues have developed antioxidant defense mechanisms to protect themselves from high concentrations of ROS. Although biological and pathological roles of ROS have previously been elucidated, so far only limited knowledge exists regarding ROS-mediated generation of DNA breaks and base lesions occurring at low frequency in intact skin cells. This study was therefore designed to probe a newly adapted pulsed-field gel electrophoresis technique for the adequate measurement of high molecular weight DNA fragments as well as to investigate the protective role of the antioxidant enzyme catalase against H2O2-mediated damage in human dermal fibroblasts. We stably transfected and overexpressed the full-length catalase cDNA in the human dermal fibroblast cell line 1306 in culture and found that these cells are significantly more protected from cytotoxicity, overall DNA strand breaks, and 8-oxodeoxyguanine base lesions resulting from H2O2-triggered oxidative stress compared to vector-transfected 1306 cells or secondary dermal fibroblasts. This work has outlined the importance of catalase in the protection from H2O2-mediated cytotoxicity and DNA damage which--if unbalanced--even when occurring at low frequency are known to lead to genomic instability, a hallmark in carcinogenesis and premature aging.
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PMID:A newly adapted pulsed-field gel electrophoresis technique allows to detect distinct types of DNA damage at low frequencies in human dermal fibroblasts upon exposure to non-toxic H2O2 concentrations. 1054 85


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