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)

Desferrioxamine (DFO) nearly doubles alkaline phosphatase oxidative inactivation by the ascorbate system. The effect is dependent on ascorbate and desferrioxamine concentrations, exhibiting in both cases a saturation mechanism. Conversion of desferrioxamine to ferrioxamine abolishes the prooxidant action. Desferrioxamine also increases ascorbate-dependent oxygen consumption and nitroblue tetrazolium reduction. Superoxide dismutase, which blocks the desferrioxamine enhancing effect on enzyme inactivation, markedly slows down nitroblue tetrazolium reduction as well as oxygen consumption by ascorbate plus desferrioxamine, while it fails to protect against the ascorbate system alone. Therefore, in the presence of desferrioxamine, the metal-catalyzed ascorbate autooxidation becomes superoxide-dependent and thus inhibitable by superoxide dismutase. Catalase, peroxidase, and ascorbate oxidase protect alkaline phosphatase from inactivation by both ascorbate and ascorbate-desferrioxamine systems. Hemin shields the enzyme from ascorbate plus DFO attack but not from ascorbate alone. In air-saturated solution, desferrioxamine seems to mediate one electron transfer from ascorbate to oxygen, generating superoxide anions, which can either trigger a Fenton reaction or produce desferal nitroxide radicals. In the absence of oxygen, ascorbate alone is ineffective, but the ascorbate plus desferrioxamine system still inactivates the enzyme; catalase, peroxidase, and ascorbate oxidase, but not superoxide dismutase, afford protection.
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PMID:Prooxidant action of desferrioxamine: enhancement of alkaline phosphatase inactivation by interaction with ascorbate system. 215 77

Hemin (ferric protoporphyrin IX chloride) in the presence of hydrogen peroxide or tert-butyl hydroperoxide was found to cleave folic acid at the C9-N10 bond. The ferrous form of hemin was not involved in hydroperoxide-dependent folic acid degradation, as indicated by the lack of inhibition by carbon monoxide. Molecular oxygen was not required for the degradation. GSH-Mn(II) or NAD(P)H in the presence of molecular oxygen did not support hemin-mediated folic acid degradation. The degradation increased as the temperature was elevated from 10 to 70 degrees C. Ascorbic acid and azide were potent inhibitors. Superoxide dismutase and hydroxyl radical quenchers, such as ethanol, mannitol, benzoate, and dimethyl sulfoxide did not inhibit the reaction. Catalase inhibited hydrogen peroxide-supported degradation but not the tert-butyl hydroperoxide-dependent one. Thiol compounds, such as thioglycolic acid, thiourea, glutathione, cysteine, and 2-mercaptoethanol, inhibited the hydrogen peroxide-dependent degradation but supported the tert-butyl hydroperoxide-mediated one. N5-formyl tetrahydrofolic acid, but not N10-formyl folic acid, was degraded by hemin in the presence of H2O2 or TBHP. The data obtained are suggestive of a mechanism similar to N-demethylation reactions catalyzed by cytochrome P-450 and some peroxidases.
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PMID:Studies on hydroperoxide-dependent folic acid degradation by hemin. 282 Mar 6

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

White, D. C. (Rockefeller Institute, New York, N.Y.). Respiratory systems in hemin-requiring Haemophilus species. J. Bacteriol. 85:84-96. 1963.-If grown in Levinthal's medium or in proteose peptone medium with excess hemin, Haemophilus influenzae, H. aegyptius, and H. canis (H. haemoglobinophilus) form an electron-transport system consisting of six cytochromes and two respiratory flavoproteins. In proteose peptone, these species can greatly modify the composition of their electron-transport complex. With anaerobic incubation in the presence of nitrate, they produce increased amounts of cytochrome c(1) and the cytochrome oxidases a(1) and o. This anaerobic pattern is greatly exaggerated by growth under carbon monoxide, in which case large concentrations of cytochrome oxidase are produced. In the presence of the inhibitor secobarbital or of growth-limiting amounts of hemin, intermediate amounts of cytochromes and respiratory flavoproteins are formed. When only small amounts of hemin are present, these species grow but form no detectable cytochrome system. Catalase is the only hemoprotein found. Under these conditions, the addition of glucose induces the formation of a lactate oxidase flavoprotein if the system is incubated aerobically. This cytochromeless state also occurs when these species are grown in KCN or anaerobically without nitrate and with excess hemin. The ability of these species to modify the composition of the electron-transport system strongly suggests that this function unit is formed from individual components. Hemin-requiring Haemophilus species have a hemin-sparing compensatory mechanism that allows growth under conditions under which hemin-independent Haemophilus species will not grow.
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PMID:Respiratory systems in the hemin-requiring Haemophilus species. 1400 Feb 93

Artemisinin loses its antimalarial activity on prolonged exposure to erythrocytes, especially alpha-thalassemic erythrocytes. In this report, we show that the major artemisinin-inactivating factor in cytosol of normal erythrocytes was heat-labile but a heat-stable factor from alpha-thalassemic cells also played a significant role in reducing artemisinin effectiveness, which was shown to be heme released from hemoglobin (Hb). Studies of fractionated lysate from genetically normal erythrocytes revealed that the protein fraction with molecular weight greater than 100 kDa was capable of reducing artemisinin effectiveness more readily than lower molecular weight fraction. Catalase and Hb A, but not selenoprotein glutathione peroxidase, were capable of reducing artemisinin effectiveness. Hemin (ferriprotoporphyrin IX) also reduced artemisinin effectiveness in a concentration- and time-dependent manner. It is concluded that heme and heme-containing proteins in erythrocyte are largely responsible for reducing artemisinin effectiveness and may contribute to resistance of Plasmodium falciparum infecting alpha-thalassemic erythrocytes observed in vitro.
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PMID:Artemisinin effectiveness in erythrocytes is reduced by heme and heme-containing proteins. 1749 68

Antioxidant enzymes are related to oral diseases. We investigated the roles of heme oxygenase-1 (HO-1) and catalase in cadmium (Cd)-induced oxidative stress and the underlying molecular mechanism in oral cancer cells. Exposing YD8 cells to Cd reduced the expression levels of catalase and superoxide dismutase 1/2 and induced the expression of HO-1 as well as autophagy and apoptosis, which were reversed by N-acetyl-l-cysteine (NAC). Cd-exposed YD10B cells exhibited milder effects than YD8 cells, indicating that Cd sensitivity is associated with antioxidant enzymes and autophagy. Autophagy inhibition via pharmacologic and genetic modulations enhanced Cd-induced HO-1 expression, caspase-3 cleavage, and the production of reactive oxygen species (ROS). Ho-1 knockdown increased autophagy and apoptosis. Hemin treatment partially suppressed Cd-induced ROS production and apoptosis, but enhanced autophagy and CHOP expression, indicating that autophagy induction is associated with cellular stress. Catalase inhibition by pharmacological and genetic modulations increased Cd-induced ROS production, autophagy, and apoptosis, but suppressed HO-1, indicating that catalase is required for HO-1 induction. p38 inhibition upregulated Cd-induced phospho-JNK and catalase, but suppressed HO-1, autophagy, apoptosis. JNK suppression exhibited contrary results, enhancing the expression of phospho-p38. Co-suppression of p38 and JNK1 failed to upregulate catalase and procaspase-3, which were upregulated by JNK1 overexpression. Overall, the balance between the responses of p38 and JNK activation to Cd appears to have an important role in maintaining cellular homeostasis via the regulation of antioxidant enzymes and autophagy induction. In addition, the upregulation of catalase by JNK1 activation can play a critical role in cell protection against Cd-induced oxidative stress.
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PMID:MAPK/JNK1 activation protects cells against cadmium-induced autophagic cell death via differential regulation of catalase and heme oxygenase-1 in oral cancer cells. 2878 7