Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the role of the superoxide (O-2) radical in chromate-related genotoxicity, we investigated whether Cr(VI) can catalyze the Haber-Weiss cycle in vitro: O-2 + Cr(VI)----Cr(V) + O2 Cr(V) + H2O2----Cr(VI) + .OH + OH-. ESR and spin trapping techniques were utilized to monitor the O-2 (produced using xanthine/xanthine oxidase), .OH, and Cr(V) species. Superoxide dismutase as well as catalase inhibited the .OH radical radical formation, attesting to the direct involvement of O-2 and H2O2 in the process. ESR measurements also provided direct evidence for the formation of Cr(V). Kinetic measurements were consistent with the role of Cr(V) and H2O2 as intermediates in .OH formation. These results indicate that in cellular media, especially during chromate phagocytosis, the O-2 radical can become a significant source of .OH radicals and hence a significant factor in the biochemical mechanism of cellular damage due to Cr(VI) exposure.
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PMID:The role of superoxide radical in chromium (VI)-generated hydroxyl radical: the Cr(VI) Haber-Weiss cycle. 130 99

In the presence of hydrogen peroxide (H2O2), xanthine oxidase has been found to catalyze sulfur trioxide anion radical (SO3.-) formation from sulfite anion (SO3(2-)). The SO3.- radical was identified by ESR (electron spin resonance) spin trapping, utilizing 5,5-dimethyl-l-pyrroline-l-oxide (DMPO) as the spin trap. Inactivated xanthine oxidase does not catalyze SO3.- radical formation, implying a specific role for this enzyme. The initial rate of SO3.- radical formation increases linearly with xanthine oxidase concentration. Together, these observations indicate that the SO3.- generation occurs enzymatically. These results suggest a new property of xanthine oxidase and perhaps also a significant step in the mechanism of sulfite toxicity in cellular systems.
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PMID:Xanthine oxidase/hydrogen peroxide generates sulfur trioxide anion radical (SO3.-) from sulfite (SO3(2-)). 131 48

Addition of xanthine 0.42 mmol.L-1 and xanthine oxidase 5.3 nmol.L-1 (X-XO) to the culture medium increased the amplitude of ESR spectra of myocardial cells, demonstrating an increase in free radical contents; diminished the action potential parameters significantly and reduced the input impedances from 0.34 +/- 0.11 to 0.24 +/- 0.1 M omega, expressing a typical electrical appearance of membrane damage. Supplying Cu 62.5 ng.ml-1 and/or Se 173 ng.ml-1 to the medium brought all of the electric parameters and the free radical content of myocardial cells back to normal. The results indicate that both the two trace elements are able to scavenge free radicals, thus antagonizing X-XO, which induces damage to myocardial cells.
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PMID:Effects of copper and selenium on electric parameters of cultured myocardial cells damaged by xanthine-xanthine oxidase. 159 30

We have adapted the low-frequency ESR spectrometer, designed and built by H.J. Halpern, to the physiologic needs of organ preparations operating at 250 MHz. Initial studies have allowed us to detect nitroxides in an isolated perfused heart. These in situ measurements were made with nitroxides specifically designed to mimic the lipophilic nature of 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) and 2,2-dimethyl-5-hydroxy-1-pyrrolidinyloxyl (DMPO-OH). These spin labels provided information about the influence of dynamic factors of the heart, such as flow rate, different cell populations and unequal distribution between compartments on our ability to conduct and interpret spin trapping experiments. They also clarified the sacrifice in sensitivity involved in operating at the lower frequencies. To deal with this later problem, we have increased the sensitivity of the spin trapping method by synthesizing a family of 15N- and deuterium-containing DMPO analogs and by determining their ability to spin trap free radicals generated by the model superoxide system of xanthine/xanthine oxidase. Finally, since activated neutrophils are one of the few cells known to generate free radicals as part of their physiologic function, we used these phagocytic cells, as a source of superoxide.
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PMID:Use of a low-frequency ESR spectrometer: implications for spin-trapping free radicals, in situ. 164 99

Oxygen radical generation in the xanthine- and NADH-oxygen reductase reactions by xanthine oxidase, was demonstrated using the ESR spin trap 5,5'-dimethyl-1- pyrroline-N-oxide. No xanthine-dependent oxygen radical formation was observed when allopurinol-treated xanthine oxidase was used. The significant superoxide generation in the NADH-oxygen reductase reaction by the enzyme was increased by the addition of menadione and adriamycin. The NADH-menadione and -adriamycin reductase activities of xanthine oxidase were assessed in terms of NADH oxidation. From Lineweaver-Burk plots, the Km and Vmax of xanthine oxidase were estimated to be respectively 51 microM and 5.5 s-1 for menadione and 12 microM and 0.4 s-1 for adriamycin. Allopurinol-inactivated xanthine oxidase generates superoxide and OH.radicals in the presence of NADH and menadione or adriamycin to the same extent as the native enzyme. Adriamycin radicals were observed when the reactions were carried out under an atmosphere of argon. The effects of superoxide dismutase and catalase revealed that OH.radicals were mainly generated through the direct reaction of H2O2 with semiquinoid forms of menadione and adriamycin.
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PMID:Allopurinol-insensitive oxygen radical formation by milk xanthine oxidase systems. 166 14

A series of experiments have been done to investigate the role of oxygen free radicals in ischemia/reperfusion injury. The following results were found: Myocardial MDA content increased significantly after post-ischemic reperfusion in vivo and in vitro. A blockade of the xanthine oxidase pathway for free radical generation could provide effective protection against ischemia/reperfusion injury. Exogenous reactive oxygen intermediates H2O2, .OH and O2- could induce changes in the contractility and electrophysiological properties of myocardial cells similar to those seen in ischemia/reperfusion. An outburst of free radical generation was detected by ESR spectroscopy at low temperature (-173 degrees C) and with the spin trapping technique during the very early phase of reperfusion. The authors emphasize the important role of free radicals in the pathogenesis of myocardial ischemia/reperfusion injury.
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PMID:The role of oxygen free radicals in myocardial ischemia/reperfusion injury. 179 73

Cultures of Methylomonas J, an aerobic methylotrophic bacterium, were grown both in Mn-rich and Fe-rich media. Crude extracts of the cultures from the Mn-rich and Fe-rich medium showed a specific activity of 12.2 and 0.6 units/mg by a cytochrome c-xanthine oxidase method and 19.4 and 1.3 units/mg by an ESR method, respectively. We isolated Mn-SOD and Fe-SOD from the bacteria grown in the Mn-rich and Fe-rich mediums, respectively. Specific activity and metal contents of the Mn-enzyme were 2,250 units/mg/g-atom Mn and Mn = 0.98 and Fe = 0.12 (g-atoms/mol dimer), while those of the Fe-enzyme were 61 units/mg/g-atom Fe and Mn = 0.02 and Fe = 1.08. No difference of physicochemical properties of the Fe- and Mn-enzymes were detected. Furthermore, enzyme activity was restored by dialysis of an apoprotein obtained from the Fe-enzyme with either manganese sulfate or ferrous ammonium sulfate.
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PMID:Isolation of Mn-SOD and low active Fe-SOD from Methylomonas J; consisting of identical proteins. 190 19

For direct measurement of the ESR signal of superoxide anion (O2-) produced in biological samples, O2- generated at a physiological pH was trapped in alkaline media instead of by a rapid freezing method, and then its signal was measured by ESR spectroscopy at 77 K. A reaction mixture for O2- generation, such as xanthine oxidase-xanthine and neutrophils, was incubated at a physiological pH (pH 7.0-7.5) for a suitable reaction period (30s), then an aliquot (300 microliters) was pipetted out and squirted into 600 microliters of 0.5 M NaOH to stabilize O2- (pH-jump). The alkaline mixture was promptly introduced into an ESR tube and frozen by dipping the tube directly into a cooling liquid. A typical signal of O2- was detected by ESR spectroscopy and the amount of trapped O2- was measured quantitatively at 77 K. The back reaction of O2- generation from H2O2 was negligible in 0.5 M NaOH. To avoid any artificial spectrum due to autoxidation of biological samples by the pH-jump procedure, the background spectrum should be subtracted from the obtained spectrum. This pH-jump method should be widely available for direct demonstration of O2- production in biological systems at physiological pH, because an advantage of this method is the simple operation for trapping O2- without the use of any rapid-mixing apparatus as compared with the rapid freezing method.
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PMID:Direct measurement of superoxide anion produced in biological systems by ESR spectrometry: a pH-jump method. 196 91

The antiperoxidant action of berbamine (Ber) was demonstrated by colorimetric estimation of malondialdehyde (MDA) formation, and the scavenging effect of Ber on O2- was investigated by chemiluminescence method and ESR-spin trapping technique. Ber 11-100 mumol/L remarkably inhibited MDA formation induced by incubating mice liver homogenate at 37 degrees C with vibration for 1 h. Ber 1-100 mumol/L and 0.2-0.6 mmol/L effectively scavenged O2- in alkaline DMSO and xanthine/xanthine oxidase systems respectively. The results show that Ber is an antioxidant.
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PMID:[Antioxidant effect of berbamine]. 196 56

Incubation of rat liver microsomes with 1-propanol and 1-butanol in the presence of NADPH and of the spin trapping agent 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) allowed the detection of free radical intermediates tentatively identified as 1-hydroxypropyl and 1-hydroxybutyl radical, respectively. Microsomes isolated from rats treated chronically with ethanol (EtOH) or with the combination of starvation and acetone treatment (SA), exhibited a two-fold increase in the ESR signal intensity as compared to untreated controls, whereas no increase was observed in phenobarbital-induced (PB) microsomes. Consistently, in reconstituted membrane vesicles, ethanol-inducible cytochrome P450IIE1 was twice as active as phenobarbital-inducible P450IIB1 in producing 1-butanol free radicals. In the microsomal preparations from EtOH and SA pretreated rats the addition of antibodies against cytochrome P450IIE1, but not of preimmune IgGs, lowered the ESR signal of 1-butanol radicals by more than 50%. The same antibodies decreased the free radical production by untreated microsomes by 35-40%, but were ineffective on microsomes from PB-treated animals. This indicated that cytochrome P450IIE1 is the major enzyme responsible for the free radical activation of alcohols in control and ethanol-fed rats. The generation of 1-hydroxybutyl radicals by EtOH microsomes was inhibited by 40, 48 and 68%, respectively, by the addition of isoniazid, tryptamine and octylamine, compounds known to specifically affect the NADPH oxidase activity of this isoenzyme. This effect was not due to the scavenging of the alcohol radical since none of these compounds affected the ESR signals originated from 1-butanol in a xanthine-xanthine oxidase system. When added to reconstituted membrane vesicles isoniazid, tryptamine and octylamine also decreased 1-butanol radical formation by P450IIE1 by 54, 38 and 66%, respectively. Such an inhibition corresponded to the effect exerted by the same compounds on O2- release from P450IIE1 containing vesicles. These results indicate that the capacity of cytochrome P450IIE1 to reduce oxygen is related to its ability to generate alcohol free radicals and suggest that ferric cytochrome P450-oxygen complex might act as oxidizing species toward alcohols.
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PMID:Role of ethanol-inducible cytochrome P450 (P450IIE1) in catalysing the free radical activation of aliphatic alcohols. 203 43


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