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)

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) generated in the stereoselective deamination of D-amino acids catalyzed by D-amino acid oxidase (DAAO). H2O2 readily crosses cellular membranes and damages DNA, proteins, and lipids. The scarcity of DAAO substrates in mammalian organisms and its co-localization with catalase in the peroxisomal matrix suggested that the cytotoxicity of ROS could be harnessed by administration of D-amino acids to tumor cells ectopically expressing DAAO in the cytoplasm. To evaluate this hypothesis, the cDNA encoding the highly active DAAO from the red yeast Rhodotorula gracilis was mutated to remove the carboxy-terminal peroxisomal targeting sequence. A clonal line of 9L glioma cells stably transfected with this construct (9Ldaao17) was found to synthesize active R. gracilis DAAO. Exposure of 9Ldaao17 cells to D-alanine resulted in cytotoxicity at concentrations that were nontoxic to parental 9L cells. Depletion of cellular glutathione further sensitized 9Ldaao17 cells to D-alanine (D-Ala). This result, combined with stimulation of pentose phosphate pathway activity and the production of extracellular H2O2 by 9Ldaao17 cells incubated with D-alanine implicates oxidative stress as the mediator of cytotoxicity. These results demonstrate that expression of R. gracilis DAAO in tumor cells confers chemosensitivity to D-alanine that could be exploited as a novel cancer gene therapy paradigm.
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PMID:Induction of cytotoxic oxidative stress by D-alanine in brain tumor cells expressing Rhodotorula gracilis D-amino acid oxidase: a cancer gene therapy strategy. 947 75

The protective mechanisms operating in the gastrointestinal (GI) tract to counteract the potential oxidizing effects of excess free iron, was tested in rats fed with excess iron. The activities of some antioxidant enzymes, the levels of GSH and the extent of lipid peroxidation at the site of iron absorption were measured. Based on the amount of thiobarbituric acid reactive substances (TBARS) produced, it could be deduced that the duodenal segment of GI tract is resistant to iron mediated lipid peroxidation. The duodenal function as judged from the activities of marker enzymes, namely, alkaline phosphatase and Lys-Ala-dipeptidyl aminopeptidase was normal. There was depletion of GSH possibly due to the increased activities of Cu, Zn SOD and catalase. However, the activity of Gpx was decreased in the Fe fed group. It was also observed that the ratios of SOD/Gpx and Cat/Gpx had significantly increased in the treated group whereas SOD/Cat remained constant suggesting that antioxidative enzymes play a key role in rendering the intestinal mucosal cells resistant to iron induced oxidative damage in rats.
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PMID:Protective effects of antioxidant enzymes and GSH in vivo on iron mediated lipid peroxidation in gastrointestinal tract of rat. 949 52

Three metallo forms of peptide deformylase (PDF, EC 3.5.1.31) of Escherichia coli were prepared and crystallized (space group C2, diffraction limit 1.9 A) for initiating the X-ray structure determination of the metal center in correlation with the catalytic functionality of this enzyme. The native Fe2+ containing enzyme species was directly isolated from overproducing bacteria by using catalase as a buffer additive, which stabilizes the catalytic activity against oxidative destruction. The Ni2+ containing form, which is oxygen-insensitive, was obtained by metal exchange with free Ni2+ and found to be catalytically equally effective (kcat/KM = 10(5) M-1 s-1 for N-formyl-Met-Ala). The Zn2+ form, prepared from the apoenzyme or by displacement of bound Ni2+ by free Zn2+, proved virtually inactive.
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PMID:Isolation and crystallization of functionally competent Escherichia coli peptide deformylase forms containing either iron or nickel in the active site. 961 Mar 60

The role of the inflammatory cytokine interleukin 1beta (IL-1beta) as potent agonist of the PMN respiratory burst signal transduction cascade has been described. We hypothesized that this phenomenon is self-limiting and that polymorphonuclear leukocyte (PMN)-derived reactive oxygen intermediates (ROI) might provide feedback regulation on the IL-1beta surface receptor (IL-1betaR)-G-protein-effector enzyme transducing tripartite complex that ultimately leads to NADPH oxidase activation. Therefore, we separately assessed either baseline or IL-1beta-induced activation of each member of the IL-1betaR-G-protein-phospholipase D (PLD) or IL-1betaR-G-protein-phospholipase C (PLC) signaling systems in the presence or absence of one of several specific ROI scavengers/antioxidants. Purified human PMN were lipopolysaccharide primed, adhered for 2 h, and stimulated with 100 ng/mL IL-1beta with or without 1% v/v dimethyl sulfoxide, 10 mM NaN3, 30 mM L-alanine, 200 U catalase, or 300 U superoxide dismutase (SOD). To validate the use of these antioxidants, the production of O2-, H2O2, hypochlorous acid, or myeloperoxidase (MPO) in the employed experimental model was confirmed in a separate set of experiments. The expression of IL-1betaR type I or II was assessed by binding with corresponding 125I-labeled monoclonal antibodies and corrected for nonspecific binding. PLD activation was assessed by measuring phosphatidyl ethanol formation in the presence of ethanol. PLC activation was determined by quantitative measurement of diacylglycerol. The level of Galpha stimulatory and inhibitory subunits was assessed by Western blotting. IL-1betaR type I expression was significantly up-regulated in the presence of catalase and SOD. PLD activation was increased by dimethyl sulfoxide and NaN3, and PLC activation was up-regulated by NaN3, L-alanine, SOD, and catalase. After 5 min of stimulation with IL-1beta, Gialpha expression was significantly down-regulated by NaN3 and SOD, whereas SOD had an up-regulating effect on the expression of Gs alpha. Increasing concentrations of externally added authentic MPO progressively down-regulated both PLD and PLC activity. Thus, PMN-derived ROI, in addition to their role as antibacterial/fungal agents, serve as second messengers in IL-1beta signal transduction, with MPO having the most ubiquitous role as a modulator of PMN second messenger pathways.
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PMID:The role of neutrophil-derived oxidants as second messengers in interleukin 1beta-stimulated cells. 968 92

This study was designed to clarify the effects of pentoxifylline (PTX) and N-acetylcysteine (NAC) on hepatic reperfusion injury in rats. Rats were pretreated with NAC, or PTX, or combination of the drugs. In each rat, liver was isolated after twenty minutes reperfusion following thirty minutes ischemia. Plasma alanine amino transferase (ALT) activity, liver tissue glutathione (GSH) and malondialdehyde (MDA) levels, glutathione peroxidase (GPx), glutathione reductase (GSSGR), superoxide dismutase (SOD) and catalase (CAT) activities were determined. Plasma ALT activity was higher in ischemia/reperfusion groups than in control. It was decreased in the groups given NAC. Administration of NAC maintained tissue GSH levels, whereas the levels were decreased in both the ischemia/reperfusion groups treated (P < 0.05) and untreated with PTX (P < 0.01). Increases in liver MDA concentration in ischemia/reperfusion (P < 0.01) and PTX-treated groups (P < 0.05) were mitigated by administration of NAC. GPx and CAT activities were increased in the ischemia/reperfusion (P < 0.01, P < 0.05) and PTX-treated groups (P < 0.05, P < 0.001). GSSGR activities were increased in the NAC (P < 0.001) and NAC-PTX-treated groups (P < 0.01). SOD activities were higher in the ischemia/reperfusion (P < 0.01) and the PTX-treated (P < 0.01) and the NAC-PTX-treated groups (P < 0.01 ). In conclusion, short-term liver ischemia/reperfusion diminished GSH, increased MDA and induced some antioxidant enzymes. While we could not find any useful effects with PTX as we expected, our findings indicate that NAC might be useful to prevent tissue damage in hepatic ischemia/reperfusion injury.
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PMID:Pentoxifylline and N-acetylcysteine in hepatic ischemia/reperfusion injury. 972 Oct 71

Four bacterial strains were isolated from larval cultures and collectors of the scallop Pecten maximus. They showed a high level of intragroup genomic relatedness (84-95%) as determined by DNA-DNA hybridization. The cells were Gram-negative, strictly aerobic, motile, ovoid rods. They grew at temperatures from 15 to 37 degrees C and from pH 7.0 to 10, but did not grow in the absence of NaCl and required growth factors. They had the ability to use a wide variety of compounds as sole carbon source: D-mannose, D-galactose, D-fructose, D-glucose, D-xylose, melibiose, trehalose, maltose, cellobiose, sucrose, mesoerythritol, D-mannitol, glycerol, D-sorbitol, meso-inositol, succinate, propionate, butyrate, gamma-aminobutyrate, DL-hydroxybutyrate, 2-ketoglutarate, pyruvate, fumarate, glycine, L-alpha-alanine, beta-alanine, L-glutamate, L-arginine, L-lysine, L-ornithine and L-proline. They exhibited oxidase and catalase activities but no denitrification activity. The isolates did not contain bacteriochlorophyll a. The G + C content ranged from 57.6 to 58 mol%. Phylogenetic analyses of the 16S rRNA sequence revealed that these isolates belong to the genus Roseobacter. On the basis of quantitative hybridization data, it is proposed that these isolates should be placed in a new species, Roseobacter gallaeciensis. The type strain is Roseobacter gallaeciensis BS107T (= CIP 105210T).
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PMID:Roseobacter gallaeciensis sp. nov., a new marine bacterium isolated from rearings and collectors of the scallop Pecten maximus. 973 Dec 95

Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular damage that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. The RCCs are characterized by 1) high incidence of pulmonary metastasis and peritoneal invasion, 2) high incidence of tumor-associated mortality and 3) possible involvement of reactive oxygen species in carcinogenesis. The present study investigated the possible role of Tsc2 and VHL tumor suppressor genes in this model. Thirty-four Fe-NTA-induced primary RCCs and 20 other primary or metastatic tumors of rats were searched for genetic alteration in all the coding exons of both genes by polymerase chain reaction-single-strand-conformation polymorphism analysis and sequencing in conjunction with morphological evaluation. In the Fe-NTA-induced RCCs, frequency of metastasis or invasion was proportionally associated with the nuclear grade of the tumor (grades 1-3). Only one Fe-NTA-induced RCC of grade 1 revealed missense mutations with loss of heterozygosity in exon 10 of the Tsc2 gene (codons 334, GTG (Val) to GCG (Ala), and 336, TAT (Tyr) to CAT (His). No mutation was found in the VHL gene. The results suggest that 1) high-grade RCCs can develop in the absence of mutations in the Tsc2 and VHL genes in rats, and that 2) Tsc2 gene somatic mutation can nonetheless be one of the causes of non-Eker rat RCCs.
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PMID:Development of high-grade renal cell carcinomas in rats independently of somatic mutations in the Tsc2 and VHL tumor suppressor genes. 976 16

A methylotrophic yeast, Candida boidinii, was grown on various combinations of peroxisome-inducing carbon source(s) (PIC(s)), i.e. methanol, oleate and D-alanine, and the regulation of peroxisomal proteins (both matrix and membrane ones) and organelle proliferation were studied. This regulation was followed (1) at the protein or enzyme level by means of the peroxisomal enzyme activity and Western analysis; (2) at the mRNA level by Northern analysis; and (3) at the organelle level by direct observation of peroxisomes under a fluorescent microscope. Peroxisomal proliferation was followed in vivo by using a C. boidinii strain producing a green fluorescent protein having peroxisomal targeting signal 1. When multiple PICs were used for cell growth, C. boidinii induced specific peroxisomal proteins characteristic of all PIC(s) present in the medium, responding to all PIC(s) simultaneously. Thus, these PICs were considered to induce peroxisomal proliferation independently and not to repress peroxisomes induced by other PICs. Next, the sensitivity of the peroxisomal induction to glucose repression was studied. While the peroxisomal induction by methanol or oleate was completely repressed by glucose, the D-alanine-induced activities of D-amino acid oxidase and catalase, Pmp47, and the organelle proliferation were not. These results indicate that peroxisomal proliferation in yeasts is not necessarily sensitive to glucose repression. Lastly, this regulation was shown to occur at the mRNA level.
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PMID:Regulation of peroxisomal proteins and organelle proliferation by multiple carbon sources in the methylotrophic yeast, Candida boidinii. 979 89

Redox-active forms of iron are known to catalyze free radical mediated peroxidative reactions. There is scanty information on such effects at the sites of iron absorption. This was tested in iron-deficient WKY female rats supplemented for 15 days with FeSO4 equivalent to 8 mg of iron (D+) and compared with iron deficient (D) and iron adequate (C) rats. The levels of intestinal MDA and protein carbonyls and the activities of various antioxidant enzymes were estimated. As markers of functional integrity, the activities of alkaline phosphatase and Lys-Ala-dipeptidyl aminopeptidase were evaluated. In addition, we measured the concentrations of ferritin, transferrin, and ceruloplasmin levels in serum and in intestinal mucosa. It was observed that correction of iron deficiency resulted in significant increase in MDA and protein carbonyl formation. Activities of both alkaline phosphatase and Lys-Ala-dipeptidyl aminopeptidase were significantly decreased in D+ compared to C. The increase in catalase and decrease in Gpx was found to be sensitive to iron administration. Neither iron deficiency nor its correction had any effect on the activity of SOD and GSH levels. Iron supplementation has resulted in decreased mobilization of stored iron as reflected by increased mucosal ferritin level and decreased serum ceruloplasmin ferroxidase activity contributing to greater peroxidative stress in the intestine. These results suggest that iron-deficient intestine of rat is more susceptible to iron-mediated peroxidative damage and functional impairment during correction of deficiency with iron.
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PMID:Iron-deficient intestine is more susceptible to peroxidative damage during iron supplementation in rats. 980 Oct 65

The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with antioxidants was investigated. Adult female Sprague-Dawley rats were injected sc with 5 micromol CdCl2/kg/day, 5 times a week, for up to 22 weeks. Serum alanine amino transferase and lactate dehydrogenase activities were elevated after 9 weeks of Cd administration, indicating hepatic damage. Renal toxicity, indicated by elevation in urinary lactate dehydrogenase activity and protein, was also observed around this time. Chronic Cd administration resulted in a gradual rise in hepatic as well as renal cortex glutathione levels. In spite of this, lipid peroxidation increased in both tissues, particularly during the second half of the Cd exposure period. Depletion of glutathione following buthionine sulfoximine administration at the end of Week 5, or inhibition of catalase by aminotriazole at the end of Week 7, resulted in the development of acute nephrotoxicity within 6 h. Coadministration of antioxidants, N-acetylcysteine (50-100 mg/kg, sc), or vitamin E (100-150 mg/kg, sc) with Cd, starting from the early phases of Cd exposure, controlled Cd-induced lipid peroxidation and protected the animals against hepatic as well as renal toxicity. A Japanese hepatoprotective drug, Stronger Neo-Minophagen C, containing glycyrrhizin, glycine, and cysteine, was also effective in reducing the chronic Cd nephrotoxicity. In conclusion, oxidative stress appears to play a major role in chronic Cd-induced hepatic and renal toxicity since inhibition of components of the antioxidant defense system accelerated and administration of antioxidants protected against Cd toxicity.
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PMID:Oxidative stress as a mechanism of chronic cadmium-induced hepatotoxicity and renal toxicity and protection by antioxidants. 993 Dec 85


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