Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.6 (catalase)
55,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress is thought to contribute to the initiation and progression of atherosclerosis. As glutathione peroxidase-1 (Gpx1) is an antioxidant enzyme that detoxifies lipid hydroperoxides, we tested the impact of Gpx1 deficiency on atherosclerotic processes and antioxidant enzyme expression in mice fed a high-fat diet (HFD). After 12 weeks of HFD, atherosclerotic lesions at the aortic sinus were of similar size in control and Gpx1-deficient mice. However, after 20 weeks of HFD, lesion size increased further in control but not in Gpx1-deficient mice, even though plasma and aortic wall markers of oxidative damage did not differ between groups. In control mice, the expression of Gpx1 increased and that of Gpx3 decreased at the aortic sinus after 20 weeks of HFD, with no change in the expression of Gpx2, Gpx4, catalase, peroxiredoxin-6, glutaredoxin-1 and -2, or thioredoxin-1 and -2. By comparison, in Gpx1-deficient mice, the expression of antioxidant genes was unaltered except for a decrease in glutaredoxin-1 and an increase in glutaredoxin-2. These changes were associated with increased expression of the proinflammatory marker monocyte chemoattractant protein-1 in control mice but not in Gpx1-deficient mice. In summary, a specific deficiency in Gpx1 was not accompanied by an increase in markers of oxidative damage or increased atherosclerosis in a murine model of HFD-induced atherogenesis.
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PMID:Lack of the antioxidant glutathione peroxidase-1 does not increase atherosclerosis in C57BL/J6 mice fed a high-fat diet. 1650 38

Dark activation of light-inactivated glucose-6-phosphate dehydrogenase was inhibited by catalase in a broken pea chloroplast system. Partially purified glucose-6-phosphate dehydrogenase from pea leaf chloroplasts can be inactivated in vitro by dithiothreitol and thioredoxin and reactivated by H(2)O(2). The in vitro activation by H(2)O(2) was not enhanced by horseradish peroxidase, and dark activation in the broken chloroplast system was only slightly inhibited by NaCN. These results indicate that the dark activation of glucose-6-phosphate dehydrogenase may involve oxidation by H(2)O(2) of SH groups on the enzyme which were reduced in the light by the light effect mediator system.
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PMID:Inhibition by Catalase of Dark-mediated Glucose-6-Phosphate Dehydrogenase Activation in Pea Chloroplasts. 1666 32

Some uncouplers stimulate CO(2)-dependent O(2) evolution by intact spinach chloroplasts at pH 8.6. This effect is not due to alkalinization of the stroma. The stimulation is observed only when photosynthesis has been partly inhibited by the presence of H(2)O(2), generated in a Mehler-type reaction by the broken chloroplasts which always contaminate the intact chloroplast preparations. The addition of methyl viologen increases the Mehler-type reaction and results in greater inhibition of photosynthesis. The addition of excess catalase stimulates photosynthesis by preventing accumulation of H(2)O(2). The uncouplers stimulate photosynthesis primarily by enhancing the light-activation of enzymes that are regulated by the ferredoxin-thioredoxin system, and this effect results from the influence of the uncouplers on the redox poising of the ferredoxin in the intact chloroplasts.
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PMID:Uncouplers stimulate photosynthesis in intact chloroplasts by enhancing light-activation of enzymes regulated by the ferredoxin-thioredoxin system. 1666 18

Thioredoxin (Trx) is one of the major redox-regulating proteins. It catalyzes dithiol/disulfide exchange reactions and displays many unique intracellular and extracellular activities thereby controlling multiple mammalian cell functions. In the present study we examine the effect of exogenous Trx on the expression of several antioxidant genes in human lens epithelial (HLE B3) cells. mRNA levels for gene expression were monitored by RT-PCR and real-time PCR while protein levels were measured by western blot analysis. We have found that recombinant human Trx (hTrx)-treated HLE B3 cells have a simultaneous increase in mRNA expressions of mitochondrial manganese superoxide dismutase (MnSOD), thioltranferase 1 (TTase 1) or glutaredoxin 1 (Grx1), mitochondrial thioltransferase (TTase 2) or glutaredoxin 2 (Grx2), and thioredoxin peroxidase IV (Prx IV). The increased MnSOD and TTase 1 mRNA expressions were accompanied with their respective increases in protein levels. Other antioxidant genes, including Cu/ZnSOD, catalase, glutathione peroxidase 1 (GPx1), thioredoxin reductase 1 (TrxR1), thioredoxin peroxidase III (Prx III), and gamma-glutamyl cysteine synthetase were not affected. The ability of Trx to induce selectively these antioxidant genes in the absence of oxidative stress suggest a cytokine/growth factor-like new physiological role of hTrx in HLE B3 cells. Our data also provide evidence of a strong antioxidant defense system in HLE B3 cells that can be activated by extracellular hTrx, as well as of a possible link between the thioredoxin (Trx) and glutathione (GSH) redox regulating systems in these cells.
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PMID:Thioredoxin induced antioxidant gene expressions in human lens epithelial cells. 1671 39

In intestine, 24,25(OH)(2)D(3), which is made under conditions of calcium-, phosphate-, and 1,25(OH)(2)D(3) sufficiency, inhibits the stimulatory actions of 1,25(OH)(2)D(3) on phosphate and calcium absorption. In the current work, we provide evidence that 24,25(OH)(2)D(3)-mediated signal transduction occurs mechanistically through increased H(2)O(2) production which involves binding of 24,25(OH)(2)D(3) to catalase and resultant decreases in enzyme activity. Physiological levels of H(2)O(2) mimicked the action of 24,25(OH)(2)D(3) on inhibiting 1,25(OH)(2)D(3)-stimulated phosphate uptake in isolated enterocytes. Moreover, the molecular basis of such inhibition was suggested by the presence of two thioredoxin domains in the 1,25D(3)-MARRS protein/ERp57: Exposure of cells to either 24,25(OH)(2)D(3) or H(2)O(2) gradually reduced 1,25(OH)(2)D(3) binding to 1,25D(3)-MARRS protein, between 10 and 20 min of incubation, but not to VDR. Feeding studies with diets enriched in the antioxidants vitamins C and E showed that net phosphate absorption in vivo nearly doubled relative to chicks on control diet. Antioxidant diets also resulted in increased [(3)H]1,25(OH)(2)D(3) binding to both 1,25D(3)-MARRS and VDR, suggesting benefits to both transcription- and membrane-initiated signaling pathways. Intriguingly, phosphorous content of bones from birds on antioxidant diets was reduced, suggesting increased osteoclast activity. Because mature osteoclasts lack VDR, we analyzed a clonal osteoclast cell line by RT-PCR and found it contained the 1,25D(3)-MARRS mRNA. The combined data provide mechanistic details for the 1,25(OH)(2)D(3)/24,25(OH)(2)D(3) endocrine system, and point to a role for the 1,25D(3)-MARRS protein as a redox-sensitive mediator of osteoclast activity and potential therapeutic target.
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PMID:Mechanism of 24,25-dihydroxyvitamin D3-mediated inhibition of rapid, 1,25-dihydroxyvitamin D3-induced responses: role of reactive oxygen species. 1681 36

The gastric pathogen Helicobacter pylori induces a strong inflammatory host response, yet the bacterium maintains long-term persistence in the host. H. pylori combats oxidative stress via a battery of diverse activities, some of which are unique or newly described. In addition to using the well-studied bacterial oxidative stress resistance enzymes superoxide dismutase and catalase, H. pylori depends on a family of peroxiredoxins (alkylhydroperoxide reductase, bacterioferritin co-migratory protein and a thiol-peroxidase) that function to detoxify organic peroxides. Newly described antioxidant proteins include a soluble NADPH quinone reductase (MdaB) and an iron sequestering protein (NapA) that has dual roles - host inflammation stimulation and minimizing reactive oxygen species production within H. pylori. An H. pylori arginase attenuates host inflammation, a thioredoxin required as a reductant for many oxidative stress enzymes is also a chaperon, and some novel properties of KatA and AhpC were discovered. To repair oxidative DNA damage, H. pylori uses an endonuclease (Nth), DNA recombination pathways and a newly described type of bacterial MutS2 that specifically recognizes 8-oxoguanine. A methionine sulphoxide reductase (Msr) plays a role in reducing the overall oxidized protein content of the cell, although it specifically targets oxidized Met residues. H. pylori possess few stress regulator proteins, but the key roles of a ferric uptake regulator (Fur) and a post-transcriptional regulator CsrA in antioxidant protein expression are described. The roles of all of these antioxidant systems have been addressed by a targeted mutant analysis approach and almost all are shown to be important in host colonization. The described antioxidant systems in H. pylori are expected to be relevant to many bacterial-associated diseases, as genes for most of the enzymes carrying out the newly described roles are present in a number of pathogenic bacteria.
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PMID:The diverse antioxidant systems of Helicobacter pylori. 1687 43

Plasmodium falciparum possesses a single mitochondrion with a functional electron transport chain. During respiration, reactive oxygen species are generated that need to be removed to protect the organelle from oxidative damage. In the absence of catalase and glutathione peroxidase, the parasites rely primarily on peroxiredoxin-linked systems for protection. We have analysed the biochemical and structural features of the mitochondrial peroxiredoxin and thioredoxin of P. falciparum. The mitochondrial localization of both proteins was confirmed by expressing green fluorescent protein fusions in parasite erythrocytic stages. Recombinant protein was kinetically characterized using the cytosolic and the mitochondrial thioredoxin (PfTrx1 and PfTrx2 respectively). The peroxiredoxin clearly preferred PfTrx2 to PfTrx1 as a reducing partner, reflected by the KM values of 11.6 microM and 130.4 microM respectively. Substitution of the two dyads asparagine-62/tyrosine-63 and phenylalanine-139/alanine-140 residues by aspartate-phenylalaine and valine-serine, respectively, reduced the KM for Trx1 but had no effect on the KM of Trx2 suggesting some role for these residues in the discrimination between the two substrates. Solution studies suggest that the protein exists primarily in a homodecameric form. The crystal structure of the mitochondrial peroxiredoxin reveals a fold typical of the 2-Cys class peroxiredoxins and a dimeric form with an intermolecular disulphide bridge between Cys67 and Cys187. These results show that the mitochondrial peroxiredoxin of P. falciparum occurs in both dimeric and decameric forms when purified under non-reducing conditions.
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PMID:Structural and biochemical characterization of a mitochondrial peroxiredoxin from Plasmodium falciparum. 1687 48

The reductive repair of oxidized methionine residues performed by methionine sulfoxide reductase is important for the gastric pathogen Helicobacter pylori to maintain persistent stomach colonization. Methionine-containing proteins that are targeted for repair by Msr were identified from whole-cell extracts (after cells were exposed to O(2) stress) by using a coimmunoprecipitation approach. Proteins identified as Msr-interacting included catalase, GroEL, thioredoxin-1 (Trx1), and site-specific recombinase; with one exception (Trx1, the reductant for Msr) all these proteins have approximately twofold higher methionine (Met) content than other proteins. These Met-rich proteins were purified and were shown to individually form a cross-linked adduct with Msr. Catalase-specific activity in an msr strain was one-half that of the parent strain; this difference was only observed under oxidative stress conditions, and the activity was restored to nearly wild-type levels by adding Msr plus dithiothreitol to msr strain extracts. In agreement with the cross-linking study, pure Msr used Trx1 but not Trx2 as a reductant. Comparative structure modeling classified the H. pylori Msr in class II within the MsrB family, like the Neisseria enzymes. Pure H. pylori enzyme reduced only the R isomer of methyl p-tolyl-sulfoxide with an apparent K(m) of 4.1 mM for the substrate. Stress conditions (peroxide, peroxynitrite, and iron starvation) all caused approximately 3- to 3.5-fold transcriptional up-regulation of msr. Neither the O(2) level during growth nor the use of background regulatory mutants had a significant effect on msr transcription. Late log and stationary phase cultures had the highest Msr protein levels and specific activity.
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PMID:Methionine sulfoxide reductase in Helicobacter pylori: interaction with methionine-rich proteins and stress-induced expression. 1688 52

Gram-negative anaerobes in the genus Bacteroides are the predominant members of the GI-tract microflora where they play an important role in normal intestinal physiology. Bacteroides spp. also are significant opportunistic pathogens responsible for an array of intra-abdominal and other infections. Bacteroides fragilis is the most common anaerobic pathogen and it possesses virulence factors such as a capsule and neuraminidase that contribute to its success as a pathogen. Infection occurs when organisms escape from the anaerobic colon to aerobic sites such as the peritoneum where O(2) concentrations average 6%. Thus in addition to the classic virulence factors, resistance to oxidative stress is essential and may be involved in the initiation and persistence of infection. In fact, B. fragilis is highly O(2) tolerant, surviving extended periods (>24h) of O(2) exposure without a significant affect on viability. For protection against this oxidative stress B. fragilis mounts a complex physiological response that includes induction of >28 proteins involved in detoxification of oxygen radicals, protection of macromolecules, and adaptive physiology. One experimental strategy used to characterize this oxidative stress response is the direct detection of genes and proteins induced during exposure to O(2) or H(2)O(2). The methods employed have included RNA differential display to capture unique mRNA transcripts produced during oxidative stress, and native or 2D-gel electrophoresis to isolate and identify newly formed stress-induced proteins. Using these and other approaches a wide array of genes induced by oxidative stress have been discovered. These include genes for catalase, superoxide dismutase, thioredoxin-peroxidase, p20-peroxidase, cytochrome c peroxidase, Dps, alkyl hydroperoxidase, aerobic ribonucleotide reductase, ruberythrin, starch utilization, aspartate decarboxylase, and an RNA binding protein. The genes encoding these activities fall into three regulatory classes: (1) induced by O(2) only, (2) induced by H(2)O(2) only, and (3) induced by either O(2) or H(2)O(2). Such a complex regulatory response will likely involve multiple regulators. Thus far one regulator has been identified, OxyR, which controls a subset of the class 3 genes that are induced by either O(2) or H(2)O(2). OxyR responds rapidly to oxidative stress and transcriptional analyses have shown that OxyR-controlled genes are activated by as little as 0.5% O(2) or 10 microM H(2)O(2). Maximal expression of most OxyR regulon genes was reached at 50 microM H(2)O(2) and 2% O(2). These oxidant concentrations are similar to environmental levels that would be experienced by the organisms in tissues outside of the colon suggesting that the OxyR regulon would be induced during the course of an infection.
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PMID:The complex oxidative stress response of Bacteroides fragilis: the role of OxyR in control of gene expression. 1688 6

The intraerythrocytic protozoan parasite Plasmodium falciparum is responsible for more than 500 million clinical cases of tropical malaria annually. Although exposed to high fluxes of reactive oxygen species, Plasmodium lacks the antioxidant enzymes catalase and glutathione peroxidase. Thus, the parasite depends on the antioxidant capacity of its host cell and its own peroxidases. These are fuelled by the thioredoxin system and are considered to represent the major defense line against peroxides. Five peroxidases that act in different compartments have been described in P. falciparum. They include two typical 2-Cys peroxiredoxins (Prx), a 1-Cys Prx, the so-called antioxidant protein (AOP), which is a further Prx acting on the basis of a 1-Cys mechanism, and a glutathione peroxidase-like thioredoxin peroxidase. Because of their central function in redox regulation and antioxidant defense, some of these proteins might represent highly interesting targets for structure-based drug development. In this article we summarize the present knowledge on the thioredoxin and peroxiredoxin metabolism in malaria parasitized red blood cells. We furthermore report novel data on the biochemical and kinetic characterization of different thioredoxins, of AOP, and of the classic 1-Cys peroxiredoxin of P. falciparum.
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PMID:Thioredoxin networks in the malarial parasite Plasmodium falciparum. 1691 Jul 70


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