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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both nitric oxide (NO) and superoxide are generated by macrophages, neutrophils and endothelial cells. It has been postulated that the generation of these two radicals under physiological conditions can lead to the formation of peroxynitrite and (as a result of the homolytic lysis of this molecule) the production of hydroxyl radicals. We have used 3-morpholinosydnonimine N-ethylcarbamide (SIN-1), a sydnonimine capable of generating both NO and superoxide simultaneously, to test this hypothesis. SIN-1 (1 mM) generated superoxide and NO at rates of 7.02 microM/min and 3.68 microM/min respectively in phosphate-buffered saline, pH 7.2, at 37 degrees C. Incubation of SIN-1 with both deoxyribose and sodium benzoate resulted in the formation of malondialdehyde (MDA). In addition, the incubation of SIN-1 with sodium benzoate resulted in the production of compounds with fluorescence emission spectra characteristic of hydroxylated products. Both the production of MDA and the generation of fluorescent compounds were inhibited by the hydroxyl radical scavenger mannitol. In all the above respects, SIN-1 mimicked the production of hydroxyl radicals from the ascorbate-driven Fenton reaction. Catalase had no effect on the SIN-1-dependent generation of MDA, and superoxide dismutase was partially inhibitory. SIN-1 produces an oxidant with the properties of the hydroxyl radical by a mechanism clearly different to that of the Fenton reaction. We conclude that the simultaneous production of NO and superoxide from SIN-1 results in the formation of hydroxyl radicals.
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PMID:Production of hydroxyl radicals from the simultaneous generation of superoxide and nitric oxide. 131 May 95

We investigated the effects of H2O2 generated by glucose (G) and glucose oxidase (GO) on the isolated rabbit tracheal smooth muscle suspended in Krebs-Ringer solution. H2O2 generated by G+GO was measured with luminol-dependent chemiluminescence. G+GO in the concentrations of 1x (1.80 microM G, 0.075 U/ml GO) and 2, 4, and 8x generated 1.35, 3.2, 6.10, and 6.00 microM of H2O2, respectively. H2O2 produced relaxation of rabbit tracheal smooth muscle, relaxed acetylcholine (ACh)-precontracted muscle, and reduced muscle responsiveness to ACh. These effects were concentration dependent. H2O2, however, produced contraction of guinea pig tracheal smooth muscle. Catalase completely inhibited the H2O2-induced relaxation of ACh-precontracted tracheal smooth muscle. H2O2-induced relaxation was greater in preparations with intact epithelium (65%) than in those denuded of epithelium (40%). The relaxant effects of H2O2 in the presence of an inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine), an inhibitor of guanylate cyclase (methylene blue), an inhibitor of cyclooxygenase (indomethacin), and an ATP-sensitive K+ channel blocker (glipizide) were 44, 44, 39, and 48%, respectively. H2O2-induced relaxation in the presence of indomethacin in preparations with denuded epithelium was 29%. These results suggest that H2O2-induced relaxation of tracheal smooth muscle is partly epithelium dependent and is mediated by inhibitory arachidonic acid metabolites, epithelium-derived relaxing factor (nitric oxide), ATP-sensitive K+ channels, and the synthesis and release of prostaglandins from epithelium and the underlying smooth muscle.
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PMID:Mechanism of H2O2-induced modulation of airway smooth muscle. 133 2

Our objective was to determine whether hydroxylamine is a possible intermediate in the oxidative conversion of L-arginine to nitric oxide. Vasorelaxation by hydroxylamine is known to be mediated by nitric oxide. The vasorelaxant properties of hydroxylamine were examined using rat aortic rings and an isolated rat lung perfusion model. Hydroxylamine and acetylcholine were equally effective in relaxing norepinephrine-contracted intact aortic rings, whereas only hydroxylamine relaxed aortic rings with endothelium removed. This endothelium-independent vasorelaxation by hydroxylamine indicated that the hydroxylamine-converting enzyme is not localized solely within endothelial cells. Catalase, an enzyme known to oxidize hydroxylamine to nitric oxide, was present in homogenates of intact and endothelium-denuded rings. Cyanamide, another catalase substrate and a known precursor of nitroxyl (HNO), was not a vasorelaxant of aortic rings or of isolated, hypoxia-constricted lungs. These results suggest that free nitroxyl is not an intermediate in the oxidation of hydroxylamine to nitric oxide. An overall pathway for the oxidative conversion of L-arginine through an hydroxylamine intermediate to nitric oxide is proposed.
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PMID:Hydroxylamine is a vasorelaxant and a possible intermediate in the oxidative conversion of L-arginine to nitric oxide. 250 70

The interactions between nitric oxide (NO), H2O2, and catalase were investigated. H2O2 did not cause detectable breakdown of NO in the absence of catalase, but did cause NO breakdown in the presence of catalase. Catalase bound NO, and NO rapidly and reversibly inhibited catalase with a Ki of 0.18 microM. The significance of these results for NO cytotoxicity is discussed.
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PMID:Reversible binding and inhibition of catalase by nitric oxide. 755 49

Nitric oxide (NO) induces a covalent modification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from various tissues. This phenomenon, which has previously been interpreted as an auto-ADP-ribosylation, is in fact a covalent binding of NAD+ to the enzyme. In the present study, we show that 3-morpholino-sydnonimine (SIN-1) is much more efficient than sodium nitroprusside (SNP) in stimulating the covalent labelling of GAPDH from cultured striatal neurones in the presence of [adenylate-32P]NAD+ (877 +/- 110 and 266 +/- 33% increase in NAD(+)-labelling induced by maximally effective concentrations of SIN-1 and SNP respectively). The difference in the efficacy of both NO-generating compounds could be due to the additional release of superoxide by SIN-1, since superoxide dismutase and the nitrone 5,5'-dimethyl pyrroline-1-oxide markedly inhibited the SIN-1-induced covalent binding of NAD+ to GAPDH. Catalase and selective scavengers of hydroxyl radicals, mannitol and dimethyl sulphoxide, did not alter the SIN-1-induced covalent modification of GAPDH, ruling out the involvement of hydroxyl radicals in this phenomenon. Supporting further a role of oxygen free radicals in the NAD+ linkage to GAPDH, pyrogallol, a superoxide generator, which alone was ineffective, potentiated the SNP-evoked response. The NAD+ linkage to neuronal GAPDH measured in the presence of NO and superoxide probably involves sulphydryl groups, since the radiolabelling of the protein was reversed by exposure to HgCl2 and prevented by pretreatment with the alkylating agent N-ethylmaleimide. Moreover, the NO-induced inhibition of GAPDH activity was enhanced by pyrogallol, which was ineffective alone. In conclusion, the present study indicates that superoxide anions potentiate NO-induced covalent NAD(+)-linkage to GAPDH and enzyme inactivation.
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PMID:Oxygen free radicals enhance the nitric oxide-induced covalent NAD(+)-linkage to neuronal glyceraldehyde-3-phosphate dehydrogenase. 763 7

3-Morpholinosydnonimine (SIN-1) is widely used to generate nitric oxide (NO(x).) and superoxide radical (O2-.). The effect of SOD on the toxicity of SIN-1 is complex, depending on what is the ultimate species responsible for toxicity. SIN-1 (< 1 mM) was only slightly toxic to HepG2 cells. Copper, zinc superoxide dismutase (Cu,Zn-SOD) or manganese superoxide dismutase (Mn-SOD) increased the toxicity of SIN-1. Catalase abolished, while sodium azide potentiated, this toxicity, suggesting a key role for H2O2 in the overall mechanism. Depletion of GSH from the HepG2 cells also potentiated the toxicity of SIN-1 plus SOD. Although Me2SO, sodium formate, and mannitol had no protective effect, iron chelators, thiourea and urate protected the cells against the SIN-1 plus Cu,Zn-SOD-mediated cytotoxicity. The cytotoxic effect of Cu,Zn-SOD but not Mn-SOD, showed a biphasic dose response being most pronounced at lower concentrations (10-100 units/ml). In the presence of SIN-1, Mn-SOD increased accumulation of H2O2 in a concentration-dependent manner. In contrast, Cu,Zn-SOD increased H2O2 accumulation from SIN-1 at low but not high concentrations of the enzyme, suggesting that high concentrations of the Cu,Zn-SOD interacted with the H2O2. EPR spin trapping studies demonstrated the formation of hydroxyl radical from the decomposition of H2O2 by high concentrations of the Cu,Zn-SOD. The cytotoxic effect of the NO donors SNAP and DEA/NO was only slightly enhanced by SOD; catalase had no effect. Thus, the oxidants responsible for the toxicity of SIN-1 and SNAP or DEA/NO to HepG2 cells under these conditions are different, with H2O2 derived from O2-. dismutation playing a major role with SIN-1. These results suggest that the potentiation of SIN-1 toxicity by SOD is due to enhanced production of H2O2, followed by site-specific damage of critical cellular sites by a transition metal-catalyzed reaction. These results also emphasize that the role of SOD as a protectant against oxidant damage is complex and dependent, in part, on the subsequent fate and reactivity of the generated H2O2.
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PMID:Increased cytotoxicity of 3-morpholinosydnonimine to HepG2 cells in the presence of superoxide dismutase. Role of hydrogen peroxide and iron. 767 15

The reactivity and toxicity of nitric oxide is modest in comparison to oxidants derived from nitric oxide. Exposure of Escherichia coli to 1 mM nitric oxide under aerobic or anaerobic conditions did not decrease viability of the bacteria. Peroxynitrite (1 mM), the reaction product of superoxide and nitric oxide, was completely bactericidal after 5 s. The nitrovasodilator, 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), slowly decomposes to release both nitric oxide and superoxide and thereby produces peroxynitrite. SIN-1 killed E. coli in direct proportion to its concentration with an LD50 of 0.5 mM. Copper, zinc superoxide dismutase (50-400 units/ml) provided substantial but not complete protection against SIN-1 killing. Catalase (500-10,000 units/ml) partially protected in direct proportion to its concentration, while inactivated catalase was not protective. Superoxide dismutase and catalase together completely protected E. coli against SIN-1 toxicity. Oxy-hemoglobin eliminated both SIN-1 and peroxynitrite toxicity. The bactericidal activity of SIN-1 was further enhanced by pterin plus xanthine oxidase. Pterin plus xanthine oxidase alone or together with Fe3+ ethylenediamine tetraacetate produced no significant decrease in E. coli viability. Hydrogen peroxide was not directly toxic to the bacteria, but E. coli pretreated with hydrogen peroxide were more susceptible to peroxynitrite, SIN-1, and the aerobic oxidation products of nitric oxide. Hydrogen peroxide pretreatment did not increase significantly the toxicity of nitric oxide under anaerobic conditions. Our results suggest that peroxynitrite is far more toxic to E. coli than nitric oxide or its by products from aerobic oxidation.
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PMID:The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli. 784 Jun 33

A simple method in mice was established to screen anti-ischemic compounds. Thirteen times binding of rubber ring (1 x 1 mm, d = 42 mm) for 4.5 hrs, swelled the paws of 60% mice applied and 14 times binding swelled only of 5% mice. Critically reversible limit lay between these conditions. "All or none" rule dominated the paw swelling perhaps due to different endogenous anti-oxidants' levels of individual mice. Determination of paw reversibility at 90 min of recirculation, was proved to be suitable. Swollen paws at this time returned normal and the paws with no-reflow dropped out by muscle necrosis after several days. Intravenous (i.v.) bovine Cu, Zn-SOD and bacterial Mn-SOD (3-10 x 10(4) U/kg) or liposomal Cu, Zn-SOD (0.3-3 x 10(4) U/kg) were protective (35-50%) by 14 times binding. Allopurinol (10-100 mg/kg) and D-mannitol (3-30 mg/kg) was effective (25-55%). Catalase (i.v., up to 10(5) U/kg) showed little protection, but local injection of 100 U/kg resulted in 50% protection. Glutathione (30 mg/kg) was suppressive only by local injection suggesting the importance of administration route. Desferal, heparin and nitric oxide synthesis inhibitor showed some protection, but indomethacin, mepyramine, ascorbate, vitamin E and dexamethasone were without effect. Excess dosing of all anti-oxidants tested, dramatically decreased their effects demanding caution for therapeutic trials.
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PMID:Superoxide dismutases and anti-oxidants protected mice from no-reflow and necrotic damage induced by ischemia. 831 25

Polymorphonuclear neutrophils generate both nitric oxide and superoxide and these molecules can combine to form peroxynitrite. Neutrophils also contain myeloperoxidase which reacts with peroxynitrous acid (HOONO). On mixing myeloperoxidase with HOONO compound II was formed. Compound I could not be detected as an intermediate. The apparent second-order rate constant of formation of compound II was strongly pH-dependent (2.5 x 10(5) M-1 x s-1 at pH 8.9 and 6.2 x 10(6) M-1 x s-1 at pH 7.2). The pKa of this effect is 6.9 and it was concluded that the enzyme reacts with the protonated form of the peroxide, that is peroxynitrous acid, with a pH-independent second-order rate constant of 2.0 x 10(7) M-1 x s-1 at 12 degrees C. The interaction of HOONO with lactoperoxidase was studied for comparison. As was observed for myeloperoxidase, compound I could not be detected as an intermediate. The apparent second-order rate constant of compound II formation is pH-dependent and is 3.3 x 10(5) M-1 x s-1 at pH 7.4 and 8.4 x 10(4) M-1 x s-1 at pH 9.0. In contrast, horseradish peroxidase reacts with HOONO to form compound I, which is subsequently followed by the formation of compound II. The second-order rate constant for the formation of compound I is 3.2 x 10(6) M-1 x s-1 and is pH-dependent, the pKa for this effect is 6.8. Catalase (up to 3 microM) does not affect the rate of decomposition of peroxynitrite and no compound I formation is observed. Since nitrite may be present in the peroxynitrite preparation and to discriminate between the reaction of the enzyme with nitrite or peroxynitrite, the effect of nitrite on myeloperoxidase was studied. The dissociation constant for the myeloperoxidase-nitrite complex is pH-dependent and has values of 580 microM at pH 6.0 and 55 mM at pH 8.5.
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PMID:Interaction of myeloperoxidase with peroxynitrite. A comparison with lactoperoxidase, horseradish peroxidase and catalase. 839 11

The influence of nitric oxide on human sperm hyperactivation and capacitation, as well as its mechanism of action and its possible origin from spermatozoa were studied. Percoll-washed spermatozoa from healthy volunteers were incubated in Ham's F-10 medium supplemented or not with the nitric oxide-releasing agents, diethylamine-NONOate or spermine-NONOate, in combination or not with superoxide dismutase or catalase (scavengers for the superoxide anion and for hydrogen peroxide, respectively), or with sodium nitrate, sodium nitrite, or preincubated NONOates. Sperm hyperactivation, capacitation, and nitric oxide synthase activity were determined. High concentrations (0.3 to 1 mM) of NONOates reduced sperm motility. However, a lower concentration (0.1 mM) of the two NONOates had no effect on the percentage of sperm motility or of hyperactivation but resulted in a significant increase in sperm capacitation (24% +/- 4%) when compared to that of control spermatozoa (Ham's F-10 alone, 12% +/- 2%). Nitric oxide released by the NONOates appeared responsible for this effect because sodium nitrate or nitrite or preincubated NONOates (to exhaust the formation of nitric oxide) had no influence on sperm capacitation. Catalase, but not superoxide dismutase, abolished the capacitating action of the NONOates. No nitric oxide synthase activity was detected in spermatozoa, whether they were in their basal state or already capacitated. Furthermore, the nitric oxide synthetase inhibitor L-NG nitroarginine methyl ester did not block sperm capacitation induced by fetal cord serum ultrafiltrate. It is therefore concluded that, although spermatozoa do not possess detectable nitric oxide synthase activity, low levels of nitric oxide induce human sperm capacitation, and this action likely involves hydrogen peroxide.
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PMID:Low levels of nitric oxide promote human sperm capacitation in vitro. 857 82


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