scholarly journals Superoxide dismutase-inhibitible reduction of cytochrome c by the alloxan radical. Implications for alloxan cytotoxicity

1982 ◽  
Vol 207 (3) ◽  
pp. 609-612 ◽  
Author(s):  
C C Winterbourn
Keyword(s):  
Superoxide Dismutase ◽  
Cytochrome C ◽  
Xanthine Oxidase ◽  
Reduced Glutathione ◽  
Direct Reaction ◽  
Cytochrome C Reduction

Cytochrome c was reduced when superoxide was generated from xanthine oxidase in the presence of alloxan, and by the reaction of alloxan and with reduced glutathione. In each case, most of the reduction was inhibited by superoxide dismutase, but considerably more enzyme was required than with superoxide alone. This indicates that the superoxide dismutase-inhibitible cytochrome c reduction was mainly due to a direct reaction with the alloxan radical, and implies that other reactions that are inhibited by superoxide dismutase could be due to either alloxan radicals or superoxide.

Superoxide, Xanthine Oxidase and Platelet Reactions: Further Studies on Mechanisms by which Oxidants Influence Platelets

1981 ◽  
Vol 45 (03) ◽  
pp. 290-293 ◽  
Author(s):  
Peter H Levine ◽  
Danielle G Sladdin ◽  
Norman I Krinsky
Keyword(s):  
Superoxide Dismutase ◽  
Cytochrome C ◽  
Xanthine Oxidase ◽  
Direct Effect ◽  
Platelet Function ◽  
Experimental Conditions ◽  
Release Reaction

SummaryIn the course of studying the effects on platelets of the oxidant species superoxide (O- 2), Of was generated by the interaction of xanthine oxidase plus xanthine. Surprisingly, gel-filtered platelets, when exposed to xanthine oxidase in the absence of xanthine substrate, were found to generate superoxide (O- 2), as determined by the reduction of added cytochrome c and by the inhibition of this reduction in the presence of superoxide dismutase.In addition to generating Of, the xanthine oxidase-treated platelets display both aggregation and evidence of the release reaction. This xanthine oxidase induced aggreagtion is not inhibited by the addition of either superoxide dismutase or cytochrome c, suggesting that it is due to either a further metabolite of O- 2, or that O- 2 itself exerts no important direct effect on platelet function under these experimental conditions. The ability of Of to modulate platelet reactions in vivo or in vitro remains in doubt, and xanthine oxidase is an unsuitable source of O- 2 in platelet studies because of its own effects on platelets.

scholarly journals Superoxide modulates the activity of myeloperoxidase and optimizes the production of hypochlorous acid

1988 ◽  
Vol 252 (2) ◽  
pp. 529-536 ◽  
Author(s):  
A J Kettle ◽  
C C Winterbourn
Keyword(s):  
Superoxide Dismutase ◽  
Xanthine Oxidase ◽  
Hypochlorous Acid ◽  
Direct Reaction ◽  
Chlorination Reaction ◽  
Inactive Compound ◽  
Physiological Conditions ◽  
Oxidant Damage ◽  
Form Compound ◽  
Compound Ii

Myeloperoxidase catalyses the conversion of H2O2 and Cl- to hypochlorous acid (HOCl). It also reacts with O2- to form the oxy adduct (compound III). To determine how O2- affects the formation of HOCl, chlorination of monochlorodimedon by myeloperoxidase was investigated using xanthine oxidase and hypoxanthine as a source of O2- and H2O2. Myeloperoxidase was mostly converted to compound III, and H2O2 was essential for chlorination. At pH 5.4, superoxide dismutase (SOD) enhanced chlorination and prevented formation of compound III. However, at pH 7.8, SOD inhibited chlorination and promoted formation of the ferrous peroxide adduct (compound II) instead of compound III. We present spectral evidence for a direct reaction between compound III and H2O2 to form compound II, and for the reduction of compound II by O2- to regenerate native myeloperoxidase. These reactions enable compound III and compound II to participate in the chlorination reaction. Myeloperoxidase catalytically inhibited O2- –dependent reduction of Nitro Blue Tetrazolium. This inhibition is explained by myeloperoxidase undergoing a cycle of reactions with O2-, H2O2 and O2-, with compounds III and II as intermediates, i.e., by myeloperoxidase acting as a combined SOD/catalase enzyme. By preventing the accumulation of inactive compound II, O2- enhances the activity of myeloperoxidase. We propose that, under physiological conditions, this optimizes the production of HOCl and may potentiate oxidant damage by stimulated neutrophils.

Cytochrome c, an ideal antioxidant

2003 ◽  
Vol 31 (6) ◽  
pp. 1312-1315 ◽  
Author(s):  
M.O. Pereverzev ◽  
T.V. Vygodina ◽  
A.A. Konstantinov ◽  
V.P. Skulachev
Keyword(s):  
Superoxide Dismutase ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Xanthine Oxidase ◽  
Cytochrome Oxidase ◽  
The Other ◽  
Other Hand ◽  
O2 Reduction

Generation of Δψ (membrane potential) by cytochrome oxidase proteoliposomes oxidizing superoxide-reduced cytochrome c has been demonstrated. XO+HX (xanthine oxidase and hypoxanthine) were used to produce superoxide. It was found that the generation of Δψ is completely abolished by cyanide (an uncoupler) or by superoxide dismutase, and is enhanced by nigericin. Addition of ascorbate after XO+HX causes a further increase in Δψ. On the other hand, XO+HX added after ascorbate do not affect Δψ, indicating that superoxide does not have measurable protonophorous activity. The half-maximal cytochrome c concentration for Δψ generation supported by XO+HX was found to be approx. 1 μM. These data and the results of some other researchers can be rationalized as follows: (1) O2 accepts an electron to form superoxide; (2) cytochrome c oxidizes superoxide back to O2; (3) an electron removed from the reduced cytochrome c is transferred to O2 by cytochrome oxidase in a manner that generates ΔμH+ (transmembrane difference in electrochemical H+ potential). Thus cytochrome c mediates a process of superoxide removal, resulting in regeneration of O2 and utilization of the electron involved previously in the O2 reduction. It is important that cytochrome c is not damaged during the antioxidant reaction, in contrast with many other antioxidants.

scholarly journals Neutrophils adherent to a nonphagocytosable surface (glomerular basement membrane) produce oxidants only at the site of attachment

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 161-166 ◽  
Author(s):  
MC Vissers ◽  
WA Day ◽  
CC Winterbourn
Keyword(s):  
Superoxide Dismutase ◽  
Plasma Membrane ◽  
Cytochrome C ◽  
Basement Membrane ◽  
Horseradish Peroxidase ◽  
Cell Surface ◽  
Oxygen Uptake ◽  
Glomerular Basement Membrane ◽  
Cerium Chloride ◽  
Cytochrome C Reduction

Abstract Adherence of neutrophils to glomerular basement membrane containing immunoglobulin G aggregates was accompanied by a marked increase in oxygen uptake (eightfold). Very little of the O2 consumed was recovered as superoxide, measured by cytochrome c reduction, or as H2O2, measured with horseradish peroxidase and scopoletin. When neutrophils were incubated with the basement membrane preparation in the presence of cerium chloride to detect H2O2, electron micrographs showed cerium perhydroxide deposits in the contact area between the cells and the basement membrane, but not on the remainder of the cell surface. The results imply that superoxide is produced only where the plasma membrane is in contact with the basement membrane matrix, and that it mostly breaks down to H2O2 or undergoes other reactions at this site. The longer lifetime of H2O2 compared with that of superoxide allows some of the H2O2 produced to be detected in the medium. The results also suggest that the area of contact between the neutrophil and surfaces such as basement membrane is inaccessible to proteins in the medium, eg, cytochrome c. Circulating scavengers such as superoxide dismutase or catalase, or proteolytic inhibitors, may therefore be unable to control events occurring at this site.

scholarly journals Neutrophils adherent to a nonphagocytosable surface (glomerular basement membrane) produce oxidants only at the site of attachment

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 161-166
Author(s):  
MC Vissers ◽  
WA Day ◽  
CC Winterbourn
Keyword(s):  
Superoxide Dismutase ◽  
Plasma Membrane ◽  
Cytochrome C ◽  
Basement Membrane ◽  
Horseradish Peroxidase ◽  
Cell Surface ◽  
Oxygen Uptake ◽  
Glomerular Basement Membrane ◽  
Cerium Chloride ◽  
Cytochrome C Reduction

Adherence of neutrophils to glomerular basement membrane containing immunoglobulin G aggregates was accompanied by a marked increase in oxygen uptake (eightfold). Very little of the O2 consumed was recovered as superoxide, measured by cytochrome c reduction, or as H2O2, measured with horseradish peroxidase and scopoletin. When neutrophils were incubated with the basement membrane preparation in the presence of cerium chloride to detect H2O2, electron micrographs showed cerium perhydroxide deposits in the contact area between the cells and the basement membrane, but not on the remainder of the cell surface. The results imply that superoxide is produced only where the plasma membrane is in contact with the basement membrane matrix, and that it mostly breaks down to H2O2 or undergoes other reactions at this site. The longer lifetime of H2O2 compared with that of superoxide allows some of the H2O2 produced to be detected in the medium. The results also suggest that the area of contact between the neutrophil and surfaces such as basement membrane is inaccessible to proteins in the medium, eg, cytochrome c. Circulating scavengers such as superoxide dismutase or catalase, or proteolytic inhibitors, may therefore be unable to control events occurring at this site.

Multiple Bovine Myoglobin Inhibition of Cytochrome c Reduction by Xanthine Oxidase

Nature ◽  
1964 ◽  
Vol 201 (4922) ◽  
pp. 928-929 ◽  
Author(s):  
J. R. QUINN ◽  
A. M. PEARSON
Keyword(s):  
Cytochrome C ◽  
Xanthine Oxidase ◽  
Cytochrome C Reduction

scholarly journals Xanthine oxidase and neutrophil infiltration in intestinal ischemia

1986 ◽  
Vol 251 (4) ◽  
pp. G567-G574 ◽  
Author(s):  
M. B. Grisham ◽  
L. A. Hernandez ◽  
D. N. Granger
Keyword(s):  
Superoxide Dismutase ◽  
Xanthine Oxidase ◽  
Reduced Glutathione ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Neutrophil Infiltration ◽  
Mucosal Injury ◽  
Ischemia And Reperfusion ◽  
Reactive Oxygen Metabolites ◽  
Oxygen Metabolites

A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radical may mediate the mucosal injury produced by reperfusion of ischemic intestine. Xanthine oxidase has been proposed as the primary source of these reduced O2 species because pretreatment with xanthine oxidase inhibitors such as allopurinol or pterin aldehyde prevent postischemic mucosal injury. Another potential source of oxygen radicals is the inflammatory neutrophil. To ascertain whether neutrophils could play a role in the pathogenesis of ischemia-reperfusion injury in the small bowel we examined the effect of ischemia and reperfusion on neutrophil infiltration and tissue levels of reduced glutathione, superoxide dismutase, and catalase. Our studies demonstrate that reperfusion of ischemic intestines results in a dramatic increase (1,800%) in neutrophil infiltration and a concurrent loss of reduced glutathione and superoxide dismutase of 60 and 30%, respectively. Catalase activity was unaffected by ischemia-reperfusion. Pretreatment with allopurinol or administration of superoxide dismutase prevented the influx of neutrophils and retarded the drop in reduced glutathione levels. These results suggest a relationship among xanthine oxidase-generated oxy radicals, neutrophil extravasation, and mucosal damage. We propose that ischemia and reperfusion results in xanthine oxidase-generated, superoxide-dependent accumulation of inflammatory neutrophils in the mucosa where neutrophil-derived reactive oxygen metabolites mediate and/or exacerbate intestinal injury.

scholarly journals Reactions of Adriamycin with haemoglobin. Superoxide dismutase indirectly inhibits reactions of the Adriamycin semiquinone

1982 ◽  
Vol 203 (1) ◽  
pp. 155-160 ◽  
Author(s):  
D A Bates ◽  
C C Winterbourn
Keyword(s):  
Superoxide Dismutase ◽  
Cytochrome C ◽  
Xanthine Oxidase ◽  
Detrimental Effect ◽  
Reversible Reaction ◽  
Red Cell ◽  
Rapid Reaction ◽  
The Right

The Adriamycin semiquinone produced by the reaction of xanthine oxidase and xanthine with Adriamycin has been shown to reduce both methaemoglobin and cytochrome c. In air, but not N2, both reactions were inhibited by superoxide dismutase. With cytochrome c, superoxide formed by the rapid reaction of the semiquinone with O2, was responsible for the reduction. However, even in air, methaemoglobin was reduced directly by the Adriamycin semiquinone. Superoxide dismutase inhibited this reaction by removing superoxide and hence the semiquinone by displacing the equilibrium: Semiquinone + O2 in equilibrium or formed from quinone + O2-. to the right. This ability to inhibit indirectly reactions of the semiquinone could have wider implications for the protection given by superoxide dismutase against the cytotoxicity of Adriamycin. Oxidation of haemoglobin by Adriamycin has been shown to be initiated by a reversible reaction between the drug and oxyhaemoglobin, producing methaemoglobin and the Adriamycin semiquinone. Reaction of the semiquinone with O2 gives superoxide and H2O2, which can also react with haemoglobin. Catalase, by preventing this reaction of H2O2, inhibits oxidation of oxyhaemoglobin. Superoxide dismutase, however, accelerates oxidation, by inhibiting the reaction of the semiquinone with methaemoglobin by the mechanism described above. Although superoxide dismutase has a detrimental effect on haemoglobin oxidation, it may protect the red cell against more damaging reactions of the Adriamycin semiquinone.

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