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)

Evidence suggests that the helminth antioxidant enzyme superoxide dismutase (SOD) may play a role in parasite's defense against the cellular immune mechanisms of the host. In order to investigate this for the human parasite Onchocerca volvulus, the enzyme activity was characterized, the release of SOD by the parasite was examined, and a complete cDNA encoding the O. volvulus SOD was identified. The SOD activity in adult O. volvulus was found to be 8.1 +/- 4.2 U/mg of protein. A Cu/Zn-containing enzyme was demonstrated by its sensitivity towards cyanide, azide, and hydrogen peroxide. Isoelectric focusing, combined with an enzyme activity assay, revealed two activities at pI 6.8 and 7.6, with both activities inhibited by KCN. Adult parasites, maintained in vitro, released SOD into the culture medium, which was detected by enzyme activity. In parallel, lactate production was measured to ensure the viability of the parasite. Oligonucleotides (based upon conserved sequences in the SOD genes of other organisms) and the polymerase chain reaction were used to identify a portion of the SOD gene from O. volvulus genomic DNA. A cDNA library was constructed in lambda unizapII and screened with the genomic polymerase chain reaction fragment. A complete cDNA encoding the Cu/Zn SOD was identified, and its nucleotide sequence was determined. Southern blot hybridization experiments indicated that the Cu/Zn SOD is encoded by a single-copy gene with at least one intron.
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PMID:Characterization and molecular cloning of a Cu/Zn superoxide dismutase from the human parasite Onchocerca volvulus. 203 66

The intracellular steady-state concentrations of hydrogen peroxide or superoxide anion were increased by inhibiting either catalase, glutathione peroxidase, or superoxide dismutase activities. Catalase was inhibited with aminotriazole while glutathione peroxidase activity was blocked by eliminating reduced glutathione after addition of either iodoacetamide diethylmaleate or phorone. The concentration of aminotriazole that stimulated chemiluminescence in 50% (60 mM) was very similar to the Ki for catalase activity (70 mM). Cyanide, an inhibitor of both catalase and superoxide dismutase, stimulated chemiluminescence in 50% at a concentration (0.15 mM) which is much closer from the Ki for superoxide dismutase (0.25 mM) than from the Ki for catalase (15 microM). The superoxide dismutase inhibitor diethyldithiocarbamate also increased chemiluminescence six- to ten-fold. Depletion of reduced glutathione stimulated spontaneous chemiluminescence when its concentration decreased below 4.5 mumol X g liver-1. The results shown herein suggest that the changes in the intracellular steady-state concentration occurring after inhibition of any antioxidant enzyme are responsible for the increased spontaneous chemiluminescence. Spontaneous chemiluminescence from intact cells may be used as a noninvasive method for monitoring intracellular free radical metabolism.
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PMID:Increased spontaneous chemiluminescence from liver homogenates and isolated hepatocytes upon inhibition of O2- and H2O2 utilization. 302 9

Because hyperoxia induces early injury to lung endothelial cells and since tolerance to hyperoxia is correlated with increased lung antioxidant enzyme activity, we measured superoxide dismutase, catalase and glutathione peroxidase in both fresh isolates and primary cultures of endothelial cells from pig pulmonary artery and aorta. Cultured endothelial cells were studied at confluency and up to 5 days thereafter under control or hyperoxic conditions. In both types of confluent cell, total and cyanide-insensitive superoxide dismutase increased when compared to fresh cells. The most conspicuous postconfluency change in both types of endothelial cell was a marked decrease in glutathione peroxidase, which could be prevented by the addition of selenomethionine to culture media. A 5-day exposure to hyperoxia resulted in a 2-fold increase in cyanide-insensitive superoxide dismutase in both aortic and pulmonary artery endothelial cells. In view of a similar decrease in DNA in both types of cells despite some differences in enzyme levels, oxygen cytotoxicity could not be related to a particular antioxidant enzyme profile.
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PMID:Effects of culture conditions and hyperoxia on antioxidant enzymes in pig pulmonary artery and aortic endothelium. 711 52

The sensitivity of the microaerophilic protozoan Trichomonas vaginalis to oxygen and products of its reduction, and the antioxidant defences employed by this organism, were investigated. Studies revealed that this amitochondrial flagellate is sensitive to oxygen tensions above those experienced in situ in the vagina (i.e. > 60 microM) and that metronidazole-resistant strains (CDC 85 and IR78) were more sensitive to elevated oxygen levels than a metronidazole-sensitive isolate (1910). In the presence of radical scavengers, inactivation of organisms at 60 microM oxygen was significantly lessened. Investigation of the antioxidant enzymes present in this organism revealed that activities of peroxide-reducing enzymes (e.g. catalase and general peroxidase) were not detectable, but that a cyanide-insensitive, azide-sensitive superoxide dismutase was present in cell extracts. Measurement of thiol-cycling enzymes indicated that NADPH could drive the reduction of oxidized glutathione (thiol reductase); however, the corresponding peroxidase activity was not detected. Analysis of thiols in whole cells of T. vaginalis indicated that glutathione was absent, but high levels of other thiols, propanethiol, methanethiol and H2S, were present. No significant differences were detected in thiol levels or antioxidant enzyme activities on comparison of metronidazole-sensitive and resistant strains. These results indicate that the sensitivity of T. vaginalis to oxygen above physiological levels is due to the lack of adequate peroxide-reducing enzymes and radical-scavenging mechanisms.
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PMID:Antioxidant defences in the microaerophilic protozoan Trichomonas vaginalis: comparison of metronidazole-resistant and sensitive strains. 795 98

Because fetal rat lungs have lower baseline levels of both surfactant and antioxidant enzymes than full-term newborn rats, we questioned whether prematurely delivered rats might be more susceptible to O2 toxicity than those born at term. In the present studies, prematurely delivered rats (gestational d 21 of 22) and full-term rat pups were simultaneously put in > 95% O2 after birth. Surprisingly, we found that the preterm rats were not more susceptible to O2-induced lung damage and lethality than full-term newborns, but, in fact, the composite percentage of survival was even greater in the preterm pups from 7 to 9 d in hyperoxia and were similar thereafter up to 14 d in high O2. In addition, the preterm rats showed significantly decreased lung wet/dry weight ratios and consistently less severe pathologic evidence of pulmonary edema compared with term rats at 6 and 8 d of O2 exposure. The premature pups demonstrated the capability of inducing pulmonary antioxidant enzyme responses to hyperoxia by 3 d, and had significantly elevated copper-zinc superoxide dismutase, catalase, and glutathione peroxidase activities (and lung surfactant contents) at 6 d of O2 exposure compared with the term rats in O2. The rates of lung total O2 consumption and cyanide-resistant O2 consumption at d 6 in hyperoxia were not different for preterm versus term pups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative responses of premature versus full-term newborn rats to prolonged hyperoxia. 816 59

Effect of immobilization on antioxidant enzyme synthesis by growing and non-growing cell culture of Aspergillus niger 26 was studied. Entrapped cells showed a greater than 1.5-fold increase in the superoxide dismutase (SOD) activity and a moderate elevation in catalase activity. The immobilization did not cause changes in the spectrum of SOD isoenzymes. The observed increase in SOD activity required de novo synthesis of this enzyme, because it was suppressed by inhibitors of the transcription and translation. The addition of various viscous substances (agar, Na-alginate and pectin) stimulated the SOD synthesis. Despite these results, it was found that the changes in SOD activity are induced in response to growth in the state of immobilization rather than to presence of alginate. Immobilized A. niger cells exhibited about a 4- to 5-fold higher level of cyanide-resistant respiration. This latter phenomenon might use as an indicator of intracellular oxy-intermediate generation in cell culture growing under stress conditions. The results are discussed relative to association between physiological stress caused by immobilization and oxidative stress.
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PMID:Comparison of antioxidant enzyme biosynthesis by free and immobilized Aspergillus niger cells* 1077 Oct 58

Our previous results indicated that 3-d-old dark-grown chilling-sensitive maize (Zea mays L.) seedlings did not survive 7 d of 4[deg]C chilling stress, but 69% of them survived similar stress when the seedlings were either preexposed to 14[deg]C for 3 d or pretreated with 0.1 mM H2O2 for 4 h at 27[deg]C (T.K. Prasad, M.D. Anderson, B.A. Martin, C.R. Stewart [1994] Plant Cell 6: 65-74) or 1 mM abscisic acid (ABA) for 24 h at 27[deg]C (M.D. Anderson, T.K. Prasad, B.A. Martin, C.R. Stewart [1994] Plant Physiol 105: 331-339). We discovered that chilling imposed oxidative stress on the seedlings. Since H2O2 accumulated during the periods of both acclimation and nonacclimation, we concluded that H2O2 had dual effects at low temperature: (a) During acclimation, its early transient accumulation signals the induction of antioxidant enzymes such as catalase 3 and peroxidase to scavenge H2O2; and (b) at 4[deg]C in nonacclimated seedlings, it accumulates to damaging levels in the tissues because of low levels of these and perhaps other antioxidant enzymes. Three-day-old seedlings pretreated with H2O2 (a mild oxidative stress) or ABA showed induced chilling tolerance. In the present study, we investigated whether mitochondria are a target for chilling-induced oxidative stress and, if so, what differences do acclimation, H2O2, or ABA make to protect mitochondria from irreversible chilling injury. The results indicated that chilling, in general, impairs respiratory activity, the cytochrome pathway of electron transport, and ATPase activity regardless of the treatment. In pretreated seedlings, the activities of catalase 3 and peroxidase in the mitochondria increased severalfold compared with control and nonacclimated seedlings. The increases in these antioxidant enzymes imply that mitochondria are under oxidative stress and such increases could initiate a protective mechanism in the mitochondria. Mitochondrial respiration is partially cyanide resistant during chilling stress and also after the 1st d of recovery. Upon further recovery over 3 d, in contrast to nonacclimated seedlings, the mitochondria of acclimation-, H2O2-, and ABA-treated seedlings showed the following recovery features. (a) The mitochondrial respiration changed from a cyanide-resistant to a cyanide-sensitive cytochrome pathway, (b) cytochrome oxidase activity recovered to control levels, (c) the ability of mitochondria to generate ATP was regained, and (d) the antioxidant enzyme activities remained at or above control levels. Based on these results, we conclude that chilling impairs mitochondrial function and that chilling-induced oxidative stress seems to be a factor, at least in part, for causing possible irreversible damage to the mitochondrial membrance components. Acclimation, H2O2, and ABA provide a protective mechanism by inducing antioxidant enzymes to protect mitochondria from irreversible oxidative damage that is absent in nonacclimated seedlings. Therefore, we conclude that the ability of the seedlings to recover from chilling injury is, at least in part, due to the ability of the mitochondria to resume normal function.
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PMID:Acclimation, Hydrogen Peroxide, and Abscisic Acid Protect Mitochondria against Irreversible Chilling Injury in Maize Seedlings. 1223 29

Chloroacetonitrile (CAN) is a disinfection by-product of chlorination of drinking water. Epidemiological studies indicate that it might present a potential hazard to human health. The present work provides an evidence for CAN activation to cyanide (CN-) by myeloperoxidase (MPO)/hydrogen peroxide (H2O2)/chloride (Cl-) system in vitro. Optimum conditions for the oxidation of CAN to CN- were characterized with respect to pH, temperature and time of incubation as well as CAN, MPO, H2O2 and KCl concentrations in incubation mixtures. The kinetic parameters governing the reaction; maximum velocity (Vmax) and Michaelis-Menten constant (Km) were assessed. Oxidation of CAN to CN- by NaOCl alone was shown. Addition of the MPO inhibitors; sodium azide (NaN3), 4-amino benzoic acid hydrazine (ABAH) or indomethacin to the reaction mixtures resulted in a significant decrease in the rate of CAN oxidation. Inclusion of the antioxidant enzyme catalase (CAT) in the incubation mixtures resulted in a significant decrease in the rate of CAN oxidation and CN- formation. Addition of the sulfhydryl compounds; glutathione (GSH), N-acetyl-L-cysteine (NAC), L-cysteine or D-penicillamine significantly enhanced the rate of CN- release. In conclusion, MPO/H2O2/Cl- system has the ability of oxidizing CAN to CN-. The present results represent a novel pathway for CAN activation and might be important in explaining CAN-induced toxicity.
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PMID:Myeloperoxidase-catalyzed oxidation of chloroacetonitrile to cyanide. 1468 62

Although, oxidative stress response, which protects organisms from deleterious effects of reactive oxygen species (ROS), has been extensively studied in pro- and eukaryotes, the information about filamentous fungi is fragmentary. We investigated the effect of two ROS-generating agents (paraquat, PQ, and H2O2) on cellular growth and antioxidant enzyme induction in 12 fungal species. Our results indicate that exposure of fungal spores or mycelia to PQ and H2O2 promoted oxidative stress, as evidenced by remarkable inhibition of spore germination and biomass production; stimulation of cyanide-resistant respiration; accumulation of oxidative modified proteins. Cell responses against both superoxide and peroxide stresses include enhanced expression of superoxide dismutase (SOD) and catalase, however, the extent was different: treatment with PQ increased mainly SOD, whereas exogenous H2O2 led to enhanced catalase. We also found that G6PD has a role in the mechanism of protection against superoxide and peroxide stresses. The activation of antioxidant enzyme defence was blocked by the translation inhibitor, cycloheximide, suggesting that there was de novo enzyme synthesis.
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PMID:Oxidative stress response of filamentous fungi induced by hydrogen peroxide and paraquat. 1583 99

Neuronal death following necrotic insults involves the generation of reactive oxygen species (ROS). We investigated the effects of antioxidant gene therapy on ROS accumulation after exposure to either sodium cyanide, kainic acid or oxygen glucose deprivation (OGD). Specifically, we generated herpes simplex virus-1 amplicon vector expressing the gene for the antioxidant enzyme CuZnSOD. Overexpression of this gene in primary hippocampal cultures resulted in increased enzymatic activity of the corresponding protein. CuZnSOD significantly protected hippocampal neurons against sodium cyanide insult and the subsequent lipid peroxidation. However, it did not protect against OGD- or kainic-acid-induced toxicity. Moreover, CuZnSOD significantly worsened the toxicity, hydrogen peroxide accumulation and lipid peroxidation induced by kainic acid. As a possible explanation for this surprising worsening, CuZnSOD overexpression increased glutathione peroxidase activity in the presence of sodium cyanide but had no effect on catalase or glutathione peroxidase activity in the presence of kainic acid. Thus, cells were unlikely to be able to detoxify the excess hydrogen peroxide produced as a result of the CuZnSOD overexpression. These studies can be viewed as a cautionary note concerning gene therapy intervention against necrotic insults.
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PMID:Gene therapy in the nervous system with superoxide dismutase. 1663 May 87


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