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)

To investigate the possibility that human polymorphonuclear leukocytes (PMN) elaborate sufficient amounts of hydrogen peroxide (H2O2) and other radicals of reduced oxygen to be autotoxic and retard directed cell movement and phagocytosis, the rate of ingestion of opsonized lipopolysaccharide-paraffin oil particles and movement through Nuclepore filters were studied. Ingestion rates were increased under anaerobic conditions and in normal aerobic conditions in the presence of extracellular catalase but not superoxide dismutase (SOD) or scavengers of singlet oxygen or hydroxyl radicals. Conversely, ingestion rates were decreased when cells were exposed to H2O2 or a superoxide anion (O2-)-H2O2 generating system of xanthine-xanthine oxidase. Catalase, but not SOD, prevented the effect and also enhanced the directed movement of PMN in normal aerobic conditions. PMN from volunteers administered 1600 U/day of the membrane lipid antioxidant alpha-tocopherol were hyperphagocytic but killed Staphylococcus aureus 502A less effectively than controls, suggesting that less H2O2 was available to damage PMN or kill bacteria. H2O2-dependent stimulation of the hexose monophosphate shunt, H2O2 release from phaogytizing PMN, and fluoresceinated concanavalin A cap formation promoted by H2O2 damage to microtubules were all diminished, but the release of O2- from phagocytizing PMN was not diminished in the vitamin E group. These results support the hypothesis that directed movement and phagocytosis by PMN are attenuated by autooxidative damage to the cell membrane by endogenously derived H2O2 and that the administration in vivo of vitamin E may prevent this damage by scavenging H2O2.
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PMID:Autooxidation as a basis for altered function by polymorphonuclear leukocytes. 87 28

The effects of Zn2+ in mimicking insulin in vivo and in vitro are further characterized. Like insulin, Zn2+ stimulated the conversion of [U-14C]-, [1-14C]-, and [6-14C]glucose to lipids in rat adipocytes. Maximum stimulation of lipogenesis was 55-80% of maximum insulin response after preincubation (30 min at 37 degrees C) of adipocytes with ZnCl2 (0.4 mM). Under these conditions, the half-maximum effect was achieved at 0.17 +/- 0.02 mM of ZnCl2. Similarly, an insulinlike effect of Zn2+ was observed on the oxidation of glucose by both pathways, glycolytic and hexose monophosphate shunt. In contrast, unlike insulin, Zn2+ did not inhibit lipolysis but rather exhibited a slight lipolytic activity. Also, the effect of Zn2+ on hexose influx did not exceed 14 +/- 3% that of insulin. The stimulatory effects of Zn2+ were not related to generation of H2O2. Catalase (100 micrograms/ml) did not inhibit Zn(2+)-stimulated glucose oxidation and its incorporation into lipids. Zn2+ had an additive effect on either insulin- or vanadate-stimulated conversion of [1-14C]glucose to fat, and together, the effect was approximately 140% of the maximum rate of lipogenesis. Chelation of intracellular Zn2+ by the cell-permeable chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine did not significantly affect the ability of insulin to stimulate lipogenesis. Adipocytes derived from STZ rats were largely refractory to the modulating action of insulin. In contrast, the effect of Zn2+ on lipogenesis in these cells was more pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulinlike effects of zinc ion in vitro and in vivo. Preferential effects on desensitized adipocytes and induction of normoglycemia in streptozocin-induced rats. 162 74

The addition of the polyamines, spermine and spermidine, to human neutrophils caused a depression of the hexose-monophosphate (HMP) shunt activity of neutrophils stimulated with latex particles but not of unstimulated cells. The effect was dependent on the presence of bovine serum and was not observed when normal human serum was substituted for bovine serum. The polyamine oxidase (PAO) in bovine serum was probably responsible for generating the activity since normal human serum lacks PAO. A role for PAO was further supported by the finding that partially purified bovine PAO in the presence of polyamines similarly mediated inhibition of HMP shunt activity in stimulated neutrophils. Catalase failed to prevent the inhibitory effects of the PAO-polyamine system suggesting that H2O2 is not the responsible product. In addition, our results show that human pregnancy serum known to contain PAO activity in the presence of polyamines mediated a similar inhibition of the respiratory burst.
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PMID:Inhibition of the respiratory burst of human neutrophils by the polyamine oxidase-polyamine system. 309 15

N-(2-Mercaptoethyl)-1,3-diaminopropane (WR-1065) is the free thiol form of the radio- and chemoprotector S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721). Interest currently exists in the clinical use of WR-2721 and WR-1065 as radio- and chemoprotectors of normal tissues. However, measurement of plasma levels of WR-1065 has proven difficult, due to rapid drug oxidation. Therefore, we studied factors influencing the oxidation of WR-1065, in Hepes-buffered saline as well as in tissue culture media containing 10% fetal bovine serum. The rate of oxygen consumption by WR-1065, as determined using the Clark oxygen electrode system, was faster in medium plus serum than in Hepes-buffered saline. That this effect is largely due to the presence of trace metal ions in tissue culture media and serum was indicated by the observation that addition of Cu2+ or Fe3+ to buffer stimulated oxygen consumption. Addition of KCN inhibited the reaction of WR-1065 with oxygen, and this effect was dependent on KCN concentration. That KCN blocked WR-1065 oxidation to the disulfide was verified using Ellman's reagent to quantitate the free thiol form. The rate of oxygen consumption was shown to be affected by temperature as well as concentration of WR-1065. Catalase reduced the rate of oxygen consumption of WR-1065, indicating that peroxide is formed in this system. Superoxide dismutase had a stimulatory effect. WR-1065 was found to stimulate the hexose monophosphate shunt in A549 cells. Since this stimulation was prevented by the presence of catalase, it appeared to be due to the response of the cells to peroxide, formed as a result of WR-1065 autooxidation.
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PMID:Factors influencing the oxidation of the radioprotector WR-1065. 334 Jul 31

Incubation of guinea pig pulmonary macrophages with N-formylmethionylphenylalanine (FMP) resulted in 1) a rapid increase in O2 consumption and 2) an accumulation of superoxide anion and hydrogen peroxide in the extracellular medium. The accumulation of superoxide anion and hydrogen peroxide was completely prevented in the presence of superoxide dismutase and catalase, respectively. FMP-stimulated O2 consumption and superoxide anion and hydrogen peroxide accumulation were proportional to the macrophage concentration, showed similar dependence on FMP concentration, had nearly identical kinetics, and were partially abolished by antimycin A, an inhibitor of mitochondrial respiration. FMP also stimulated a three- to fourfold increase in hexose monophosphate shunt (HMS) activity. Catalase had no effect on the amount of glucose oxidized by the HMS, indicating that removal of hydrogen peroxide was without effect on the observed HMS activity. Since FMP is similar in structure to the oligopeptides of bacterial metabolism, its ability to stimulate the release of these microbiocidal products of oxygen metabolism may be important in vivo.
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PMID:Release of oxygen products from lung macrophages by N-formyl peptides. 626 93

Quinone drugs are used extensively as anti-neoplastic agents. The mechanism of their actions and the reasons for their unfavorable side effects are not well understood. Mitomycin C (MC) is an N-heterocyclic quinone with chemotherapeutic action against solid tumors. Previous research has led to the development of a model for drug activation involving NADPH reduction of the drug via microsomal mixed-function oxidases. We tested the possibility that NADPH is provided from the hexose monophosphate shunt (HMPS). The MC did indeed increase HMPS activity aerobically, while not affecting Kreb's cycle activity. Anaerobic stimulation of the shunt is also predicted by the model. However, under hypoxic conditions no HMPS or Kreb's activity was observed in MC-treated or untreated samples. Other investigators have documented the involvement of reactive oxygen species in microsomal systems in vitro. The oxygen requirement for MC stimulation of HMPS suggests oxygen radical involvement. We carried out experiments using [14C]-formate as a scavenger for hydrogen peroxide. There was no apparent change in H2O2 production when MC was added. Catalase is known to be involved in peroxide metabolism in vivo; however, addition of the catalase inhibitor sodium azide did not alter endogenous or MC-stimulated shunt activity. The microsomal inhibitor SKF-525A (10(-3) M) prevented MC stimulation of the HMPS, which is consistent with the model implicating microsomal enzymes in MC metabolism. Overall, we have shown the oxygen dependence of endogenous and MC-stimulated shunt activity, and the results provide evidence for MC activation of oxidative metabolism by a mechanism which involves microsomes.
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PMID:Effects of mitomycin C on metabolism in a rat liver preparation. 643 9

1. The luminol-dependent chemiluminescence of rat thymocytes responding to concanavalin A can be resolved into glucose-dependent and glucose-independent portions. 2. The glucose-dependent portion, supported by D-glucose and D-mannose oxidation, is inhibited by catalase (200 microgram/ml), amobarbital (1 mM) and hexose analogues that block D-glucose uptake. Thus concanavalin A may activate, transiently, an NAD(P)H oxidase that utilizes reducing equivalents derived from the oxidation of exogenous glucose to give dismutation products of O2- (including H2O2) as its major products. 3. The glucose-independent portion is inhibited by eicosa-5,8,11,14-tetraynoic acid but not by indomethacin. It may therefore be associated with the conversion of hydroperoxy intermediates of arachidonic acid metabolism to hydroxy products by the lipoxygenase pathway. 4. Preincubation of thymocytes for 18 h in serum-free medium enhances the subsequent chemiluminescent response to concanavalin A severalfold and evokes the response at a lower threshold concentration. The incorporation of [3H]thymidine by preincubated cells is similarly enhanced at low doses of concanavalin A, whereas the response to optimal doses is unaltered. 5. Catalase does not inhibit the enhanced incorporation of [3H]thymidine obtained in response to concanavalin A, but instead amplifies the response to low doses in the same manner as preincubation.
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PMID:Concanavalin A-induced chemiluminescence in rat thymus lymphocytes. Its origin and role in mitogenesis. 697 84

Lipid peroxidation products and antioxidant enzyme activities were studied in the rat testis following exposures to cigarette smoke, polychlorinated biphenyls (PCBs), or polychlorinated naphthalenes (PCNs). Three hours after a single 1-hour period of smoke inhalation, the levels of fluorescent chromolipids and thiobarbituric acid-reactive species (TBARS) were markedly increased in the testis (+49%, P < 0.01, and +43%, P < 0.05, respectively). Twelve hours after daily smoking for 1 hour, for 1, 5, or 10 days, such an increase was not found. Activities of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione transferase (GSH-Tr), or hexose monophosphate shunt (HMS) were not affected immediately, 3 hours, or 12 hours after a single smoking session. Twelve hours after smoking for 5 days, the activity of catalase was decreased (-16%, P < 0.05). Smoking exposures had no consistent effects on serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), or testosterone concentrations. Single i.p. injections of PCB or PCN mixtures resulted in decreases in testicular SOD activity 1 day after the exposures (-14%, P < 0.05, and -51%, P < 0.01, respectively). Catalase activity also decreased after both exposures (-30 to -42%, P < 0.05, at days 1-7 after PCB exposure, and -37 to -43%, P < 0.05, at days 3-7 after PCN exposure). Ninety days after the PCN exposure, activities of GSH-Px and GSH-Tr were decreased in the testis (-20%, P < 0.05, and -26%, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipid peroxidation and antioxidant enzyme activities in the rat testis after cigarette smoke inhalation or administration of polychlorinated biphenyls or polychlorinated naphthalenes. 798 4