Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Artemisinin is an effective antimalarial agent, and its action on the malarial parasite is suggested to be mediated by oxidative processes. Since malarial parasites contain a high concentration of hemin, and hemin may induce the formation of reactive oxygen species, we investigated the interaction of artemisinin, iron and hemin. We used erythrocyte membrane-bound Ca2+ pump ATPase (basal) and calmodulin (CaM)-activated Ca2+ pump ATPase as our model. Membranes were incubated with artemisinin in the presence or absence of iron-ascorbate or hemin at 37 degrees for 1 hr. Following incubation, ATPase activity was measured. Our results showed that artemisinin (500 microM) had no effect on ATPase activities. However, artemisinin enhanced the inhibitory effect of iron (50 microM)-ascorbate (500 microM) on ATPase activity (46.3 +/- 3.9 vs 63 +/- 2.1% for basal; 57.2 +/- 2.5 vs 74.8 +/- 2.1% for CaM-activated). Desferrioxamine (DFO, 200 microM) blocked significantly the effect of iron-ascorbate-artemisinin on ATPases (P < 0.01). Hemin inhibited ATPase activity in a concentration-dependent fashion. Artemisinin enhanced hemin (10 microM)-induced inhibition of basal (36.0 +/- 6.0 vs 73.7 +/- 3.0%) and CaM-activated Ca2+ pump ATPase (31.6 +/- 2.8 vs 70.0 +/- 1.5%). Iron chelators (DFO, ferene, 8-hydroxyquinoline, 1,10-phenanthroline, and 1,2-dimethyl-3-hydroxypyrid-4-one) had no effect on artemisinin plus hemin-induced enzyme inhibition. Catalase (2000 U/mL) had a minor effect on the artemisinin-hemin or hemin-mediated effect. Thiourea (1 mM) had no effect. However, superoxide dismutase (500 U/mL) and dithiothreitol blocked artemisinin-hemin or hemin-mediated ATPase inhibition significantly (P < 0.001). In conclusion, these results suggest that, in our model, artemisinin enhances the damage of hemin-induced ATPases via oxidation of thiol groups on the enzymes. Free iron or hydroxyl radical does not seem to be involved. This interaction between artemisinin and hemin may contribute to the antimalarial action of artemisinin against malarial parasites.
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PMID:Enhancement of hemin-induced membrane damage by artemisinin. 808 Apr 46

When Escherichia coli was incubated with xanthine oxidase and acetaldehyde, the killing of E. coli was accelerated by iron-EDTA but inhibited by hematin or hemoglobin. On the other hand, when E. coli was incubated with human neutrophils in the presence of phorbol myristate acetate (PMA), all of these iron species at concentrations of a few micromolar accelerated the inactivation of neutrophils and in so doing protected the E. coli from being killed by the neutrophils. The inactivation of the neutrophils was accompanied by an increase in lipid peroxidation and by a decrease in viability measured with trypan blue. This inactivation was inhibited by scavengers such as deoxyribose, mannitol, or thiourea. Desferrioxamine B and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) both inhibited the inactivation mediated by iron-EDTA, but had no effect on the hematin- or hemoglobin-mediated inactivation. Vanadium (vanadyl ion), an effective Fenton reagent, behaved in the same way as iron-EDTA relative to the effects of DMPO on neutrophil inactivation. These results led us to conclude that neutrophils were inactivated during PMA stimulation by OH radicals in the presence of iron-EDTA and by some other oxidizing species when hematin or Hb is present. Ascorbate enhanced the inactivation of neutrophils mediated by these iron species. Catalase was very effective in inhibiting neutrophil inactivation. Superoxide dismutase was not as effective but the combination with catalase was most effective.
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PMID:The effect of hemoglobin, hematin, and iron on neutrophil inactivation in superoxide generating systems. 813 43

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

We investigated the mechanism of hydrogen peroxide (H2O2) action on myocardial injury in relation to hydroxyl radical (.OH) formation. Isolated rat hearts were perfused with a concentration of H2O2 (300 microM) known to produce cardiac injury. Perfusion of H2O2 for 15 min caused severe myocardial dysfunction, morphological damage, ATP depletion, and lipid peroxidation. Hydrogen peroxide concentration in the coronary effluent was reduced approximately 40% reflecting a myocardial H2O2 consumption of 12.7 +/- 0.9 mumol/15 min/g wet tissue (n = 12). One of the .OH-generated derivatives, 2,3-dihydroxybenzoic acid (2,3-DHBA), formed from reaction with salicylic acid, was detected in the coronary effluent by high-performance liquid chromatography at 23.16 +/- 4.05 nmol/15 min/g wet tissue. Catalase (200 U/ml, n = 6) added to the perfusate attenuated all parameters of myocardial injury by eliminating H2O2 from the perfusate, and thus .OH was not detected in the effluent. Deferoxamine (5 mM, n = 7) added to the perfusate reduced morphological damage and lipid peroxidation, but not dysfunction or ATP depletion. Deferoxamine significantly reduced .OH production; 2,3-DHBA was 5.22 +/- 3.56 nmol/15 min/g wet tissue. The present study provides evidence that .OH is produced in the H2O2-perfused heart. The adverse H2O2-mediated myocardial outcomes documented in this study appear to arise from both .OH-dependent and .OH-independent mechanisms.
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PMID:Demonstration of hydroxyl radical and its role in hydrogen peroxide-induced myocardial injury: hydroxyl radical dependent and independent mechanisms. 839 52

Free radical generation, 2'-deoxyguanosine (dG) hydroxylation and DNA damage by vanadium(IV) reactions were investigated. Vanadium(IV) caused molecular oxygen dependent dG hydroxylation to form 8-hydroxyl-2'-deoxyguanosine (8-OHdG). During a 15 min incubation of 1.0 mM dG and 1.0 mM VOSO4 in phosphate buffer solution (pH 7.4) at room temperature under ambient air, dG was converted to 8-OHdG with a yield of about 0.31%. Catalase and formate inhibited the 8-OHdG formation while superoxide dismutase enhanced it. Metal ion chelators, DTPA and deferoxamine, blocked the 8-OHdG formation. Incubation of vanadium(IV) with dG in argon did not generate any significant amount of 8-OHdG, indicating the role of molecular oxygen in the mechanism of vanadium(IV)-induced dG hydroxylation. Vanadium(IV) also caused molecular oxygen-dependent DNA strand breaks in a pattern similar to that observed for dG hydroxylation. ESR spin trapping measurements demonstrated that the reaction of vanadium(IV) with H2O2 generated OH radicals, which were inhibited by DTPA and deferoxamine. Incubation of vanadium(IV) with dG or with DNA in the presence of H2O2 resulted in an enhanced 8-OHdG formation and substantial DNA double strand breaks. Sodium formate inhibited 8-OHdG formation while DTPA had no significant effect. Deferoxamine enhanced the 8-OHdG generation by 2.5-fold. ESR and UV measurements provided evidence for the complex formation between vanadium(IV) and deferoxamine. UV-visible measurements indicate that dG, vanadium(IV) and deferoxamine are able to form a complex, thereby, facilitating site-specific 8-OHdG formation. Reaction of vanadium(IV) with t-butyl hydroperoxide generated hydroperoxide-derived free radicals, which caused 8-OHdG formation from dG and DNA strand breaks. DTPA and deferoxamine attenuated vanadium(IV)/t-butyl-OOH-induced DNA strand breaks.
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PMID:Vanadium(IV)-mediated free radical generation and related 2'-deoxyguanosine hydroxylation and DNA damage. 857 99

Electrophoretic mobility shift, DNA strand breakage assays and electron spin resonance (ESR) spin trapping were used to investigate the activation of nuclear transcription factor (NF)-kappa B, DNA strand breakage and 2'-deoxyguanosine hydroxylation induced by Cr(IV), as well the role of free radical reactions in these processes. Incubation of synthesized Cr(IV)-glutathione complex with cultured Jurkat cells resulted in activation of DNA binding activity of NF-kappa B. Cr(VI) is also able to induce NF-kappa B activation through Cr(V) and Cr(IV) intermediates generated during the reduction of Cr(VI) by the cells. Cr(III) did not cause observable NF-kappa B activation due to its inability to cross cell membranes. Cr(IV)-induced NF-kappa B activation is dose-dependent. Catalase inhibited the activation while superoxide dismutase enhanced it. The metal chelator, deferoxamine, and hydroxyl (.OH) radical scavengers, sodium formate and aspirin, also inhibited the NF-kappa B activation. Electrophoretic assays using lambda Hind III linear DNA showed that, in the presence of H2O2, Cr(IV) is capable of causing DNA strand breaks. Deferoxamine, sodium formate and aspirin inhibited the DNA strand breaks. HPLC measurements also show that .OH radical generated by the Cr(IV)-mediated reaction with H2O2 was capable of causing 2'-deoxyguanosine (dG) hydroxylation to generate 8-hydroxyguanosine (8-OHdG). The relative magnitude of 8-OHdG formation correlated with the generation of .OH radicals. ESR spin trapping measurements showed that reaction of Cr(IV) with H2O2 generated .OH radicals, which were inhibited by deferoxamine, sodium formate and aspirin. The results show that Cr(IV) can cause NF-kappa B activation, DNA strand breaks and dG hydroxylation through .OH radical-initiated reactions. This reactive chromium intermediate may play an important role in the mechanism of Cr(VI)-induced carcinogenesis. The results also suggest that the Cr(IV)-glutathione complex may be used as a model compound to study the role of Cr(IV) in Cr(VI) carcinogenicity.
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PMID:Cr(IV) causes activation of nuclear transcription factor-kappa B, DNA strand breaks and dG hydroxylation via free radical reactions. 1040 75

In the present study, the role of reactive oxygen species and the contribution of antioxidant defence in the time course of changes in acetylcholine-stimulated endothelium-dependent and sodium nitroprusside-stimulated endothelium-independent relaxation were investigated in aortic rings isolated from 6-month streptozotocin-diabetic and age-matched control rats. Although there were no significant differences in the degree of the peak relaxations produced by a single administration of acetylcholine (1 microM) or sodium nitroprusside (0.01 microM) between control and diabetic rings, the endothelium-dependent and -independent relaxant responses were more transient and the time required to reach a peak relaxation after addition of acetylcholine was shorter in diabetic vessels. Pretreatment of diabetic vessels with superoxide dismutase (100 U/ml) normalized the recovery phases of endothelium-dependent and -independent relaxations, but had no effect on the peak responses to acetylcholine and sodium nitroprusside. In the presence of diethyldithiocarbamate (5 mM), an inhibitor of superoxide dismutase, the transient nature of the relaxant response to acetylcholine or sodium nitroprusside was more marked and the peak relaxations were inhibited; these effects of diethyldithiocarbamate were more pronounced in diabetic than in control rings. Catalase, 160 U/ml, decreased the peak relaxant response to acetylcholine and accelerated fading of the relaxation in diabetic aorta. Similar results were obtained for control aorta with a higher concentration of catalase (550 U/ml). Pretreatment with 3-amino-1,2,4 triazole (5 mM), a catalase inhibitor, inhibited the peak relaxant response to acetylcholine in diabetic rings. The combination of superoxide dismutase (100 U/ml) plus 3-amino-1,2,4 triazole (5 mM) produced an increase of the transient nature of endothelium-dependent relaxation of diabetic rings greater than that with 3-amino-1,2,4 triazole alone. Neither catalase nor 3-amino-1,2,4 triazole affected the characteristics of sodium nitroprusside-induced relaxation. Desferrioxamine, an inhibitor of hydroxyl radical (.OH) production, or mannitol, a.OH scavenger, had no effect on the characteristics of either acetylcholine- or sodium nitroprusside-induced relaxation in control and diabetic rings. Biochemical measurements revealed an inhibited superoxide dismutase activity in diabetic aorta together with activated catalase. Our findings suggest that, during the chronic phase of streptozotocin-diabetes, excess superoxide (O(2)(. -)) is responsible for the enhanced transient nature of endothelium-dependent and -independent relaxation of aorta via a reduction in bioavailable concentrations of nitric oxide (NO). However, the involvement of hydrogen peroxide (H(2)O(2)) in the establishment of acetylcholine-stimulated relaxation may be increased, which is likely to account for the maintenance of the relaxant effect of acetylcholine in chronically diabetic vessels.
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PMID:Time course of changes in endothelium-dependent and -independent relaxation of chronically diabetic aorta: role of reactive oxygen species. 1076 70

The present study investigates whether reactive oxygen species (ROS) are involved in p53 activation, and if they are, which species is responsible for the activation. Our hypothesis is that hydroxyl radical (.OH) functions as a messenger for the activation of this tumor suppressor protein. Human lung epithelial cells (A549) were used to test this hypothesis. Cr(VI) was employed as the source of ROS due to its ability to generate a whole spectrum of ROS inside the cell. Cr(VI) is able to activate p53 by increasing the protein levels and enhancing both the DNA binding activity and transactivation ability of the protein. Increased cellular levels of superoxide radicals (O(2)(-).), hydrogen peroxide (H(2)O(2)), and.OH radicals were detected on the addition of Cr(VI) to the cells. Superoxide dismutase, by enhancing the production of H(2)O(2) from O(2)(-). radicals, increased p53 activity. Catalase, an H(2)O(2) scavenger, eliminated.OH radical generation and inhibited p53 activation. Sodium formate and aspirin,.OH radical scavengers, also suppressed p53 activation. Deferoxamine, a metal chelator, inhibited p53 activation by chelating Cr(V) to make it incapable of generating radicals from H(2)O(2). NADPH, which accelerated the one-electron reduction of Cr(VI) to Cr(V) and increased.OH radical generation, dramatically enhanced p53 activation. Thus.OH radical generated from Cr(VI) reduction in A549 cells is responsible for Cr(VI)-induced p53 activation.
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PMID:The role of hydroxyl radical as a messenger in Cr(VI)-induced p53 activation. 1094 36

There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet aggregation, with induction of thromboxane B2 (TXB2) production. Contrastingly, Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced platelet aggregation, and TXB2 and prostaglandin-D2 (PGD2) production. PBL extract also inhibited platelet TXB2 and PGD2 production triggered by thrombin, platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O2(*-) and *OH, and inhibits xanthine oxidase activity and the (*)OH-induced PUC18 DNA breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB2 production. Indomethacin, genistein, and PBL extract inhibited only TXB2 production, but not platelet aggregation. Catalase, superoxide dismutase, and dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation, whereas catalase and DMT inhibited the AN-induced TXB2 production. These results suggest that AN-induced platelet aggregation is associated with iron-mediated reactive oxygen species production, calcium mobilization, phospholipase C activation, and TXB2 production. PBL inhibited platelet aggregation via both its antioxidative effects and effects on TXB2 and PGD2 production. Effects of AN and PBL on platelet aggregation and AA metabolism is crucial for platelet activation in the oral mucosa and cardiovascular system in BQ chewers.
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PMID:Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase. 1197 87

Synopsis It has been proposed that oxygen free radicals are involved in skin aging. This paper describes a new method for the evaluation of oxygen free radical scavenging by cosmetic products. It is based on the measurement, by gas chromatography, of ethylene produced during the oxidation of methionine by the hydroxyl radical. OH. is produced by an iron catalyzed superoxide-driven Fenton reaction in which superoxide is obtained by photochemical oxygen reduction. The cosmetic is applied, together with methionine, riboflavine, NADH, FeCl(3) and EDTA, on a glass microfibre filter and submitted to UVA exposure through a quartz cell. Ethylene is then measured from aliquots of the atmosphere inside the cell. Catalase or Desferal completely inhibits ethylene production. SOD or high concentrations of hydroxyl radical scavengers (Mannitol, DMSO etc.) afford a partial protection. Thus the efficiency of O(2) (-)., H(2)O(2) and OH. scavengers and iron chelators can be measured. The main advantage of this test is that it is performed in conditions which simulate skin during UV exposure (e.g. air and UV exposed thin layer). Furthermore, as it is non-invasive, it can also be applied to human skin in vivo.
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PMID:Ethylene formation from methionine as a method to evaluate oxygen free radical scavenging and metal inactivation by cosmetics. 1929 Oct 46


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