Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species are generated physiologically in cells with a significant increase in certain pathological conditions, such as inflammation, cancer, aging, degenerative disease. If endogenous antioxidant systems, in our study represented by glutathione peroxidase, are exceeded by this oxidant flux, tissue injury may occur. Activity of glutathione peroxidase (GPx) was determined using Beutler's modified spectrophotometric assay in erythrocytes from autosomal dominant polycystic kidney disease patients. Activity of glutathione peroxidase was significantly (at p < 0.0001) lower there (17.75 +/- 3.69 U/g haemoglobin) compared to the control group (23.26 +/- .61 U/g Hb). Lower antioxidant enzyme defence system of ADPKD patients, here represented by GPx, can potentiate injury caused by free radicals and possibly play a role in the progression of autosomal dominant polycystic kidney disease.
Biochem Mol Biol Int 1995 Apr
PMID:Activity of the antioxidant enzyme, glutathione peroxidase, on autosomal dominant polycystic kidney disease patients. 762 19

Cyclophosphamide causes lung injury in rats through its ability to generate free radicals with subsequent endothelial and epithelial cell damage. In order to observe the protective effects of a potent anti-inflammatory antioxidant, curcumin (diferuloyl methane) on cyclophosphamide-induced early lung injury, healthy, pathogen free male Wistar rats were exposed to 20 mg/100 g body weight of cyclophosphamide, intraperitoneally as a single injection. Prior to cyclophosphamide intoxication oral administration of curcumin was performed daily for 7 days. At various time intervals (2, 3, 5 and 7 days post insult) serum and lung samples were analyzed for angiotensin converting enzyme, lipid peroxidation, reduced glutathione and ascorbic acid. Bronchoalveolar lavage fluid was analyzed for biochemical constituents. The lavage cells were examined for lipid peroxidation and glutathione content. Excised lungs were analyzed for antioxidant enzyme levels. Biochemical analyses revealed time course increases in lavage fluid total protein, albumin, angiotensin converting enzyme (ACE), lactate dehydrogenase, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, acid phosphatase, lipid peroxide levels and decreased levels of glutathione (GSH) and ascorbic acid 2, 3, 5 and 7 days after cyclophosphamide intoxication. Increased levels of lipid peroxidation and decreased levels of glutathione and ascorbic acid were seen in serum, lung tissue and lavage cells of cyclophosphamide groups. Serum angiotensin converting enzyme activity increased which coincided with the decrease in lung tissue levels. Activities of antioxidant enzymes were reduced with time in the lungs of cyclophosphamide groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1995 Jan 12
PMID:Modulation of cyclophosphamide-induced early lung injury by curcumin, an anti-inflammatory antioxidant. 775 45

Adaptation to various forms of stress has been found to be associated with increased cellular tolerance to myocardial ischemia. In this study, the effects of myocardial adaptation to oxidative stress was examined by injecting rats with endotoxin (0.5 mg/kg) and its non-toxic derivative, lipid A (0.5 mg/kg). Both compounds exerted oxidative stress within 1 h of treatment as evidenced by enhanced malonaldehyde formation. The oxidative stress disappeared steadily and progressively with time in concert with the appearance of the induction of glutathione and antioxidative enzymes that included superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. After 24 h of endotoxin or lipid A treatment, the amount of oxidative stress and antioxidant enzyme levels were significantly lower and higher, respectively, compared to those at the baseline levels. Corroborating these results, both endotoxin and lipid A provided protection against myocardial ischemia and reperfusion injury as evidenced by a significantly improved postischemic recovery of left ventricular functions. The data presented here demonstrates that a controlled amount of oxidative stress induces the expression of intracellular antioxidants that can result in enhanced myocardial tolerance to ischemia. This suggests that myocardial adaptation to oxidative stress may be a potential tool for reduction of ischemic/reperfusion injury.
Mol Cell Biochem 1995 Mar 09
PMID:Oxidative stress adaptation improves postischemic ventricular recovery. 779 47

We have investigated the effect of doxorubicin (Adriamycin) on the yeast Saccharomyces cerevisiae. Drug treatment was found to be cytotoxic to wild-type strains, in a concentration-dependent manner, whereas a petite mutant lacking the cytochrome oxidase (EC 1.9.3.1) subunit IV gene was resistant to doxorubicin. Transformation of the doxorubicin-resistant mutant with a yeast in vivo expression vector harboring the cytochrome oxidase subunit IV gene restored both respiration and sensitivity to doxorubicin. Another petite strain, with a mutation in the mitochondrial adenine nucleotide translocator (pet9), did not display doxorubicin resistance. However, in contrast to the subunit IV mutant, it possesses a functional respiratory chain. We also compared the cytotoxic effect of doxorubicin with those of daunorubicin and mitoxantrone in yeast. We found comparable levels of cytotoxicity for doxorubicin and daunorubicin, which were significantly greater than that for mitoxantrone. Finally, we constructed a yeast strain that overexpresses manganese superoxide dismutase (EC 1.15.1.1), an antioxidant enzyme present in mitochondria. Overexpression of manganese superoxide dismutase protected significantly against doxorubicin and daunorubicin cytotoxicity but only slightly against mitoxantrone cytotoxicity. Collectively, our results provide direct in vivo evidence that superoxide radicals participate in doxorubicin- and daunorubicin-induced cytotoxicity in yeast. Furthermore, these results indicate that mitochondrial respiration is a crucial factor in anthracycline, and perhaps mitoxantrone, cytotoxicity in yeast.
Mol Pharmacol 1994 Dec
PMID:Doxorubicin, daunorubicin, and mitoxantrone cytotoxicity in yeast. 780 47

The growth of fibroblasts, which were isolated from human, rabbit, rat, mouse, and chick embryos, was inhibited partially under 50% oxygen and nearly completely under 95% oxygen. There was species difference in the resistivity of these cells against oxygen-induced growth inhibition. The extent of the resistivity was in the following order: chick cells > rat cells > human cells > rabbit cells approximately mouse cells. The order of their ability to recover from oxygen-induced growth inhibition was similar to the above order of species. There was also species difference in their antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase activities, and their reduced glutathione concentration. Chick cells, having the highest resistivity against oxygen-induced growth inhibition, were at the lowest activity levels of antioxidant enzymes and at the highest concentration level of reduced glutathione. The species difference in resistivity against oxygen-induced growth inhibition seems to depend on the reduced glutathione concentration, but not on the antioxidant enzyme activities.
Comp Biochem Physiol B Biochem Mol Biol 1995 Jan
PMID:Species difference in the resistibility of embryonic fibroblasts against oxygen-induced growth inhibition. 785 38

MnSOD is an antioxidant enzyme whose decrease in activity appears involved in tumorigenesis. We had previously reported the production of a monoclonal antibody, named 35.8, against rat MnSOD. In the present paper we show that it recognizes human and mouse MnSODs, although with different detection limits. We also use the antibody for immunofluorescence studies and observed that the antibody yields a positive staining of a non-nuclear protein, in rat and human organs where high concentration of MnSOD activity have been reported, and a lack of staining in rat kidney where MnSOD activity is decreased. Two tumors, an experimental rat hepatocarcinoma and a human liver metastasis from a gastrointestinal adenocarcinoma, are found negative for immunostaining.
Biochem Mol Biol Int 1994 May
PMID:Monoclonal antibody 35.8 recognizes human, mouse and rat MnSODs in western blot and immunostaining. 808 Dec

The crystal structures of three forms of Escherichia coli thioredoxin reductase have been refined: the oxidized form of the wild-type enzyme at 2.1 A resolution, a variant containing a cysteine to serine mutation at the active site (Cys138Ser) at 2.0 A resolution, and a complex of this variant with nicotinamide adenine dinucleotide phosphate (NADP+) at 2.3 A resolution. The enzyme mechanism involves the transfer of reducing equivalents from reduced nicotinamide adenine dinucleotide phosphate (NADPH) to a disulfide bond in the enzyme, via a flavin adenine dinucleotide (FAD). Thioredoxin reductase contains FAD and NADPH binding domains that are structurally similar to the corresponding domains of the related enzyme glutathione reductase. The relative orientation of these domains is, however, very different in the two enzymes: when the FAD domains of thioredoxin and glutathione reductases are superimposed, the NADPH domain of one is rotated by 66 degrees with respect to the other. The observed binding mode of NADP+ in thioredoxin reductase is non-productive in that the nicotinamide ring is more than 17 A from the flavin ring system. While in glutathione reductase the redox active disulfide is located in the FAD domain, in thioredoxin reductase it is in the NADPH domain and is part of a four-residue sequence (Cys-Ala-Thr-Cys) that is close in structure to the corresponding region of thioredoxin (Cys-Gly-Pro-Cys), with a root-mean-square deviation of 0.22 A for atoms in the disulfide bonded ring. There are no significant conformational differences between the structure of the wild-type enzyme and that of the Cys138Ser mutant, except that a disulfide bond is not present in the latter. The disulfide bond is positioned productively in this conformation of the enzyme, i.e. it stacks against the flavin ring system in a position that would facilitate its reduction by the flavin. However, the cysteine residues are relatively inaccessible for interaction with the substrate, thioredoxin. These results suggest that thioredoxin reductase must undergo conformational changes during enzyme catalysis. All three structures reported here are for the same conformation of the enzyme and no direct evidence is available as yet for such conformational changes. The simplest possibility is that the NADPH domain rotates between the conformation observed here and an orientation similar to that seen in glutathione reductase. This would alternately place the nicotinamide ring and the disulfide bond near the flavin ring, and expose the cysteine residues for reaction with thioredoxin in the hypothetical conformation.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Biol 1994 Feb 25
PMID:Crystal structure of Escherichia coli thioredoxin reductase refined at 2 A resolution. Implications for a large conformational change during catalysis. 811 95

The effect of ischemia-reperfusion on activity, protein and m-RNA levels of catalase, copper-zinc and manganese containing superoxide dismutases and glutathione peroxidase, the enzymes that are involved in free radical detoxification was studied in rat kidney. Ischemia alone did not alter either the activities or protein levels of superoxide dismutase and glutathione peroxidase. However, catalase activity was found to be inhibited to 82% of control. The inhibition of catalase was due to the inactivation of the enzyme as there was no significant change in enzyme protein level. Reperfusion following ischemia, however, led to a significant decrease in both the activities as well as the protein levels of all the antioxidant enzymes. The observed overall decrease in total superoxide dismutase activity was the net effect of a decrease in copper-zinc superoxide dismutase while manganese superoxide dismutase activity was found to be increased following reperfusion. This observed increase manganese superoxide dismutase activity was the result of its increased protein level. The mRNA levels for catalase, superoxide dismutases, and glutathione peroxidase were observed to be increased (100-145% of controls) following ischemia; reperfusion of ischemic kidneys, however, resulted in a significant decrease in the levels of mRNAs coding for all the enzymes except manganese superoxide dismutase which remained high. These results suggest that in tissue, the down regulation of the antioxidant enzyme system could be responsible for the pathophysiology of ischemia-reperfusion injury.
Mol Cell Biochem 1993 Aug 25
PMID:Expression of antioxidant enzymes in rat kidney during ischemia-reperfusion injury. 828 74

Time-dependent changes in levels of the antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSHPOD), and catalase (CAT) after cortical focal ischemia in rat indicate that: (1) primary and peri-ischemic tissues differ in both rate and the magnitude of oxyradical-induced ischemic injury, and (2) ischemic tissue remains vulnerable to oxyradical damage as long as 72 h after ischemia since the antioxidant enzyme levels remain at or below basal levels. After 72 h, the increased levels of these enzymes are sufficient to protect tissue against oxyradical damage. GM1 ganglioside (10 mg/kg, im) further increased the already elevated levels of the enzymes after ischemia, thereby indicating the GM1 treatment increases the capacity of ischemic tissue to protect against oxyradical injury.
Mol Chem Neuropathol
PMID:Temporal changes in superoxide dismutase, glutathione peroxidase, and catalase levels in primary and peri-ischemic tissue. Monosialoganglioside (GM1) treatment effects. 846 85

The Escherichia coli sodA gene encoding the antioxidant enzyme Mn-containing superoxide dismutase (MnSOD), was cloned in the expression vector pMG36e. This vector has a multiple cloning site downstream of a promoter and Shine-Dalgarno sequences derived from Lactococcus. The protein-coding region of sodA from E. coli was amplified by the polymerase chain reaction, using a thermocycler and Taq DNA polymerase before cloning into pMG36e. When introduced into E. coli, the recombinant plasmid expressed the predicted fusion protein, both in the presence and absence of oxygen. The expression of the fusion protein in E. coli was verified by SOD assays, activity gels and Western blots. The recombinant plasmid was also introduced into Lactococcus lactis, which contains a resident SOD, and into Lactobacillus gasseri, which is devoid of SOD. Transformed lactococci expressed an active SodA fusion protein plus an active hybrid protein composed of subunits of the Lactococcus and the recombinant E. coli enzymes. Transformants of L. gasseri expressed only the fusion SodA protein, which was enzymatically active.
Mol Gen Genet 1993 May
PMID:Cloning and expression of the manganese superoxide dismutase gene of Escherichia coli in Lactococcus lactis and Lactobacillus gasseri. 851 Jun 61


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