Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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The respiratory burst is dependent on a source of glucose. We wished to investigate the effect of glucose on the superoxide production of circulating neutrophils. Superoxide production of neutrophils was significantly enhanced by glucose concentration of from 1 to 50 mmole/liter in the medium. The neutrophils from asthmatics in both the acute and remission phases showed greater production of superoxide than those of controls. When the neutrophils were made to undergo the respiratory burst, initially in the absence of glucose, and thereafter in the presence of 5 and 20 mmole/liter glucose, the rate of superoxide formation with higher glucose medium was decreased in the control cells but significantly increased in the cells of the acute asthmatics in remission. It is concluded that glucose as an energy source is potentially critical in determining the rate of the respiratory burst and that the neutrophils from asthmatic subjects in some way have an enhanced uptake or metabolism of this substrate. Glycemic status may then have some role in determining the amount of superoxide production, and therefore airway inflammation, in asthma.
Exp Mol Pathol 1995 Feb
PMID:Effect of glucose on the respiratory burst of circulating neutrophils from asthmatics. 755 86

Superoxide radical (O2-.), generated by the xanthine-xanthine oxidase system, induces significant amount (20%) of single-strand breaks in plasmid pBR322 DNA. This is almost completely inhibited by its specific scavenger, superoxide dismutase. The biological antioxidants, at near physiological concentrations show great variation in their modulation of DNA damage induced by O2-.. The thiols glutathione, cysteine and dithiothreitol do not protect DNA, instead they greatly enhance the strand-breaking activity of this free radical. However, the lipid soluble antioxidants tannic acid, butein, canthaxanthin, beta-carotene and lipoate offered significant protection to plasmid DNA against O2-.. Since O2-. is the most abundant reactive oxygen species generated, the above mentioned modulating abilities of biological antioxidants may have significant biological implications.
Biochem Mol Biol Int 1995 Feb
PMID:Variation in the modulation of superoxide-induced single-strand breaks in plasmid pBR322 DNA by biological antioxidants. 766 83

The aim of the research was to study the role played by extracellular O2-radicals, which are implicated in cardiac cell damage and the protective effect by cell-permeable, nitroxide, superoxide dismutase-mimics. Cardiomyocytes cultures from 1-day-old rats served as the test-system. Experiments were performed since 5th day in culture when > 80% of the cells were beating myocardial cells. Oxidative damage was induced by 0.5 mM hypoxanthine and 0.06 U/ml xanthine oxidase or by 10 mM glucose and 0.15 U/ml glucose oxidase. The parameters used to evaluate damages were spontaneous beating, lactate dehydrogenase release and ATP level. The rhythmic pulsation was followed microscopically. To determine the kinetics of cytosolic enzyme release from the cells, media samples were collected at various points of time and assayed for enzyme activity. To determine the cellular ATP, cells were washed with sodium phosphate buffer, scraped off and boiled for 3 min with sodium phosphate buffer. Following centrifugation the supernatant was collected and ATP was determined by the chemiluminogenic assay using firefly tails. The present results indicate that nitroxide stable free radicals in the millimolar concentration range, provide full protection without toxic side-effect. Unlike exogenously added SOD that failed to protect, exogenous catalase provided almost full protection. In addition, the metal-chelating agent dipyridyl, but not diethylene-triamine-pentaacetate or desferrioxamine, protected the cultured cells. The present results suggest that H2O2 is the predominant toxic species mediating the oxidative damage whereas extracellular superoxide radical does not contribute to cultured cardiomyocyte damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1995 Apr 26
PMID:Do nitroxides protect cardiomyocytes from hydrogen peroxide or superoxide? 767 30

The involvement of coenzyme Q (CoQ) as an antioxidant agent in several oxidative processes both in vitro and in vivo is nowadays pointed out by several biochemical and clinical studies, but the chemical mechanisms of this action are not yet unequivocally established. Electrochemistry provides very useful techniques for the analysis of the kinetics and thermodynamics, and mechanisms of chemical phenomena involving electron transfers, e.g. in the case of radical reactions. In the present study we used cyclic voltammetry to investigate the interactions between oxygen radicals and ubiquinone in aprotic medium, a condition similar to that existing in the biological membranes. The results obtained showed that ubiquinone is more easily reduced than oxygen, ruling out the possibility of an electron transfer from semiquinone to oxygen to produce superoxide radicals. On the contrary, it was demonstrated that fully reduced quinone is able to scavenge the superoxide radical, by reduction to peroxide ion, lowering actually the oxidative potential in the medium.
Mol Aspects Med 1994
PMID:Interaction between reactive oxygen species and coenzyme Q10 in an aprotic medium: a cyclic voltammetry study. 775 48

A novel technique is reported which makes use of (1) an improved method for solubilizing luminol at neutral pH along with (2) the addition of dimethyl sulfoxide to stabilize superoxide anion in the solutions in which luminescence is detected. These improvements resulted in (1) very low blank values of luminescence and (2) an approximately 6-fold increase in sensitivity of detection of peroxide and superoxide, as well as stabilizing the superoxide radical anion. The technique can also be used to evaluate the availability of antioxidants in biological homogenates and fluids.
Biochem Mol Biol Int 1994 Aug
PMID:A new technique for enhancing luminol luminescent detection of free radicals and reactive oxygen species. 780 44

The regulation of superoxide dismutase (SOD) expression was studied in 4 Entamoeba histolytica isolates. In comparison to anaerobic conditions, cultivation of the amoebae in the presence of superoxide radical anions or a ferrous iron chelator revealed substantial increase of SOD expression. Under the different culture conditions, all SOD activity could be exclusively attributed to an iron-containing type (FeSOD). Northern blot analysis revealed that FeSOD expression was regulated on the transcriptional level. Within the 5'-flanking region of the amoebic FeSOD gene, a 19-bp fragment was found with 68% sequence identity to the consensus motif of the binding site for the ferric uptake regulation gene product of Escherichia coli. Electrophoretic mobility shift assays with this 19-bp fragment and with amoebic nuclear extracts revealed specific DNA/protein complex formation. The results indicate that the regulation of E. histolytica FeSOD expression is similar to that of the manganese-containing SOD (MnSOD) of E. coli.
Mol Biochem Parasitol 1994 Oct
PMID:Induction of the iron-containing superoxide dismutase in Entamoeba histolytica by a superoxide anion-generating system or by iron chelation. 787 Jan 32

The biological properties of tumor-promoting and antipsoriatic 9-anthrones have been hypothesized to be mediated by free radical products such as the corresponding 9-anthron-10-yl radicals or by O2-, OH, and other persistent secondary radicals that are formed in the skin after topical treatment with 9-anthrones. To gain additional insights into the possible role of reactive oxygen or secondary radicals in mediating the biological effects of 9-anthrones, we have used EPR spectroscopy to investigate the formation of these species by a series of 9-anthrones or 9-anthrone dimers with known tumor-promoting and antipsoriatic activities. The effect of the 9-anthrones on keratinocyte proliferation in vitro was also investigated. 5,5-Dimethyl-1-pyrroline N-oxide was used as a spin trap to detect reactive oxygen-centered radicals in aqueous buffer/dimethylsulfoxide solutions. Super-radicals in aqueous buffer/dimethylsulfoxide solutions. Superoxide was trapped during the autoxidation of most of the 9-anthrones. For 9-anthrones that generated no detectable superoxide, evidence of anthronyl-peroxyl radical formation was found instead. In the presence of Fe3+ complexed to EDTA, but not diethylenetriaminepentaacetic acid, the hydroxyl radical was produced by all of the 9-anthrones. 9-Anthrone dimers produced oxygen-centered radicals only weakly or not at all. Direct EPR was used to detect 9-anthrone-derived secondary radicals in keratinocyte suspensions or in dimethysulfoxide solutions. These radicals were similar to those previously reported to occur in skin after topical treatment with the antipsoriatic drug anthralin (1,8-dihydroxy-9-anthrone). In contrast to the ubiquitous ability of the 9-anthrones to generate reactive oxygen radicals, only the hydroxy-substituted 9-anthrones or their dimers possessed significant secondary radical-forming ability. The ability of the 9-anthrones or dimers to form secondary radicals in keratinocytes was found to correlate with their in vitro inhibition of keratinocyte proliferation. The data suggest the possible importance of reactive dimeric intermediates in mediating the biological effects of the 9-anthrones.
Mol Pharmacol 1994 Jul
PMID:Structure-activity relationships for the formation of secondary radicals and inhibition of keratinocyte proliferation by 9-anthrones. 805 52

Superoxide radicals that result from normal cellular metabolism have been implicated as a cause of multiple age-related degenerative diseases (Halliwell, B., and Gutteridge, J. M. (1990) Methods Enzymol. 186, 1-85; Harman, D. (1988) Mol. Cell. Biochem. 84, 155-161; Ames, B. N., Shigenaga, M. K., and Hagen, T. M. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7915-7922). Manganese superoxide dismutase (MnSOD) is thought to be the sole enzymic scavenger of superoxide in mammalian mitochondria. We have investigated MnSOD activity and gene dose in mice with deletions and a duplication of the Tme (t-associated maternal effect) locus on chromosome 17. We find that MnSOD activity is significantly correlated with gene dose in these animals; animals with heterozygous deletions of Tme have 50% of normal activity, and animals with a heterozygous duplication of Tme have 150% of normal activity. These ratios of activity appear to be systemic, as they were observed in brain, heart, skeletal muscle and liver. The results support the model that basal MnSOD activity is regulated solely by cis elements, in that variation in MnSOD activity caused by altered gene dose on one chromosome is not compensated by gene activity on the other. Since gene knockouts of MnSOD have not yet been generated, the tlub2 and Thp animals may become useful models for those studying the role of mitochondrial superoxide in pathophysiological processes. A model for the maternal-lethal effect of Tme deletions is proposed.
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PMID:Mice with duplications and deletions at the Tme locus have altered MnSOD activity. 807 89

Using a lysosome-enriched "light mitochondrial" fraction of a rat liver homogenate, the effects of the reactive oxygen species hydrogen peroxide, superoxide- and hydroxyl radicals were determined. Alterations in the intralysosomal pH and the release of a lysosomal marker enzyme, N-acetyl-glucosaminidase, were used as indicators of changes in the lysosomal membrane integrity. Lipid peroxidation of the fraction was assayed by TBARS measurement. Neither superoxide radicals, generated by hypoxanthine/xanthine oxidase, nor a bolus dose of hydrogen peroxide (0.5-1.5 mM) induced any lysosomal damage. If, however, Fe(III)ADP was included in the superoxide radical-generating system, lysosomal membrane damage was detected, both as an increase in lysosomal pH and as a release of N-acetyl-glucosaminidase, but only after a lag phase of about 7 min. Lipid peroxidation, on the other hand, proceeded gradually. Lysosomes treated with hydrogen peroxide displayed similar dose-dependent alterations, albeit only if both Fe(III)ADP and the reducing amino acid cysteine were added. In the latter system, however, alterations of the lysosomal membrane stability occurred more rapidly, showing a lag phase of only 2 min. Lipid peroxidation, which proceeded faster and displayed no lag phase, levelled out within 10 min. The results indicate that neither superoxide radicals nor hydrogen peroxide are by themselves damaging to lysosomes. Available catalytically active iron in Fe(II) form, however, allows reactions yielding powerful oxidative species--probably hydroxyl radicals formed via Fenton reactions--to take place inducing peroxidation of the lysosomal membranes resulting in dissipation of the proton-gradient and leakage of their enzyme contents.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Effect of reactive oxygen species on lysosomal membrane integrity. A study on a lysosomal fraction. 814 62

Oxygen is a diradical and because of its unique electronic configuration, it has the potential to form strong oxidants (e.g. superoxide radical, hydrogen peroxide and hydroxyl radical) called oxygen free radicals or partially reduced forms of oxygen (PRFO). These highly reactive oxygen species can cause cellular injury by oxidizing lipids and proteins as well as by causing strand breaks in nucleic acids. PRFO are produced in the cell during normal redox reactions including respiration and there are various antioxidants in the cell which scavenge these radicals. Thus in order to maintain a normal cell structure and function, a proper balance between free radical production and antioxidant levels is absolutely essential. Production of PRFO in the myocardium is increased during various in vivo as well as in vitro pathological conditions and these toxic radicals are responsible for causing functional, biochemical and ultrastructural changes in cardiac myocytes. Indirect evidence of free radical involvement in myocardial injury is provided by studies in which protection against these alterations is seen in the presence of exogenous administration of antioxidants. Endogenous myocardial antioxidants have also been reported to change under various physiological as well as pathophysiological conditions. It appears that endogenous antioxidants respond and adjust to different stress conditions and failure of these compensatory changes may also contribute in cardiac dysfunction. Thus endogenous and/or exogenous increase in antioxidants might have a therapeutic potential in various pathological conditions which result from increased free radical production.
Mol Cell Biochem 1993 Dec 22
PMID:Endogenous antioxidant changes in the myocardium in response to acute and chronic stress conditions. 817 40


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