Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been previously well documented that partial pressure of oxygen (PO2) and weight-specific rate of O2 consumption in chick embryo (Gallus gallus domesticus) transiently increase midway through the 21-day in ovo incubation period. The present study found that these oxidative changes were paralleled by the concentrations of glutathione (GSH) and Zn in liver and by the specific activity of superoxide dismutase (SOD) in brain. Levels of antioxidant enzymes and their trace metal cofactors were markedly higher in liver than in brain. Hepatic catalase activity changed in parallel with the concentration of its cofactor, Fe. However, the relative abundance of metal cofactors did not appear to be the determining influence on other antioxidant enzyme activities. Rates of extra-mitochondrial hydrogen peroxide release were also much greater in liver than in brain. Taken together, the results of this initial study of embryonic chick antioxidant systems suggest that certain antioxidants may be regulated by PO2 and rate of oxidative metabolism during fetal development.
 ...
PMID:Developmental profiles of antioxidant enzymes and trace metals in chick embryo. 140 90

Endogenous hydrogen peroxide (H2O2) release from aortic endothelial cells was studied in the presence of antioxidant enzyme inhibitors, mitochondrial inhibitors, a microsomal cytochrome P-450 inhibitor, and after oxidative stress induced with H2O2 or menadione. Extracellular H2O2 generation was determined spectrofluorometrically using 3-methoxy-4-hydroxy phenylacetic acid, and intracellular H2O2 production (in or near peroxisomes) was measured indirectly using aminotriazole, which inactivates catalase in the presence of H2O2. Extracellular H2O2 release was 0.079 +/- 0.005 nmol/min/mg protein in Hanks' balanced salt solution, was constant during a 120-min incubation period, and was not affected by the cell passage number. The half-life for catalase inactivation with aminotriazole was 23 min. Inhibition of catalase, glutathione reductase, or gamma-glutamylcysteine synthetase did not change the rate of extracellular release of H2O2. Furthermore, inhibition of the mitochondrial respiratory chain (rotenone, antimycin A) or microsomal cytochrome P-450 (8-methoxypsoralen) did not change extracellular H2O2 release or intracellular H2O2 production (at peroxisomes) by endothelial cells or cells in which glutathione reductase was inactivated. When the cells were exposed to exogenous H2O2 (30 microM), extracellular H2O2 was scavenged primarily by the glutathione redox pathway. Exogenously added H2O2 (100 microM) changed intracellular H2O2 production (in or near peroxisomes) only when the glutathione redox cycle was inactivated. Menadione (20 microM), which undergoes intracellular redox cycling, increased extracellular H2O2 release almost 4-fold to 0.3 nmol/min/mg protein. Furthermore, menadione increased peroxisomal H2O2 levels and decreased the half-life for catalase inactivation in the presence of aminotriazole to 13 min. Catalase inhibition increased extracellular H2O2 release during menadione treatment, indicating that H2O2 can diffuse across the plasma membrane during oxidant stress.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Regulation of hydrogen peroxide generation in cultured endothelial cells. 154 Mar 80

Free radicals generated by a partial reduction of O2 pose a serious hazard to tissues and vital organs, especially membrane lipids, connective tissues, and the nucleic acids of cells. For protection, enzymes have evolved that specifically attack O2-, hydrogen, and organic peroxides, and repair any damage incurred to DNA. With few exceptions, antioxidant enzymes are found in all aerobic and aerotolerant anaerobic organisms. Logic assumes that a basal level of antioxidant enzyme activity is maintained at all times. This may be true. Yet cells must have ways to amplify antioxidant enzyme activity to counter sudden increases in oxygen metabolites. The full details of that regulation are slowly coming to light. Bacteria possess a series of elaborate and interacting genes that can sense specific increases in intracellular H2O2 and O2-. In higher organisms, hormones and metal ion cofactors impose pre- and posttranslational control over the genetic expression of antioxidant enzymes. Furthermore, aging, cellular differentiation, and organ specificity must also be factored into the final equation in higher organisms. This review will discuss some of the more recent findings relevant to antioxidant enzyme regulation in bacteria and higher organisms.
 ...
PMID:Regulation of antioxidant enzymes. 161 91

The importance of thioproteins, essential to the ribonucleotide reduction pathway, has been demonstrated in human primary and metastatic melanoma tissues. The thioredoxin reductase/thioredoxin and the glutathione reductase/glutathione/glutaredoxin electron transfer pathways represent alternative electron donors for ribonucleotide reductase and regulate the synthesis of deoxyribonucleotides, the substrates for DNA synthesis, in the S phase of the cell cycle. In addition to their important role in DNA synthesis and cell division, these thioproteins provide effective antioxidant defence against oxygen radicals and hydrogen peroxide. In human metastatic melanoma cells and tissues the thioredoxin reductase/thioredoxin system is located both in the cell cytosol and on plasma membranes and is under allosteric regulation by calcium. As a consequence, calcium plays an important role in determining the intracellular redox status, cell division and differentiation. Recently, the intracellular redox conditions have been shown to be important in the reaction of alkylating anti-tumour drugs such as the chloroethylnitrosoureas. In addition to previously established mechanisms, these highly reactive drugs inhibit thioredoxin reductase, glutathione reductase and ribonucleotide reductase by chloroethylation of their respective thiolate active sites. Incorporation of the 14C chloroethyl group in drug sensitive and resistant human metastatic melanoma cell lines depends on the redox status, with resistant cells being more oxic than sensitive cells. Thioredoxin reductase is 500-fold more sensitive than glutathione reductase to the newly developed nitrosourea, Fotemustine (diethyl-1-[3,2 chloroethyl]-3-nitrosoureido ethyl phosphonate). It has been shown that melanomas which respond to Fotemustine therapy contain more thioredoxin reductase whereas resistant metastases yielded the opposite result.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:New aspects in the pathophysiology of cutaneous melanoma: a review of the role of thioproteins and the effect of nitrosoureas. 184 12

We examined the effect of glucocorticoid on intrinsic glomerular antioxidant enzyme (AOE) activities. Munich-Wistar rats were treated with daily i.p. injection of vehicle or methylprednisolone [MP, 15 mg/kg body wt, (MP15)] either for three days or nine days. Glomeruli isolated from rats given MP15 had significantly higher activities of total (T-) and manganese (Mn-) superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase than vehicle-treated rats (P less than 0.05). MP15-treated rats were subjected to intrarenal arterial infusion of hydrogen peroxide (35 mumol over 1 hr). Values for urinary protein excretion rate (UprV) after hydrogen peroxide infusion were markedly lower in rats pretreated with MP15 for both three days and nine days than in untreated rats (109 +/- 18 and 55 +/- 24 vs. 416 +/- 73 micrograms/min, respectively, both P less than 0.005). To test whether the same therapeutic intervention attenuates reactive oxygen species (ROS)-mediated glomerular injury in another model, rats given a single i.v. dose of puromycin aminonucleoside (PAN) (50 mg/kg body wt) were treated with daily i.p. injection of vehicle or MP15. Two days after PAN administration, when compared to vehicle-treated controls, PAN rats given MP15 had significantly higher activities of Mn-SOD, GSH-Px and catalase. After eight days of PAN injection, T- and Mn-SOD activities were, likewise, significantly higher in MP15- than vehicle-treated PAN rats. PAN rats given MP15 also had substantially less proteinuria, compared to PAN rats given vehicle alone, UprV averaging 32.3 +/- 9.4 versus 159.0 +/- 13.8 mg/24 hr (P less than 0.05). Elevated glomerular malondialdehyde (MDA) level characteristic of PAN rats was absent in rats treated with MP15. Moreover, epithelial foot process fusion and cell vacuolization seen in vehicle-treated PAN rats were markedly attenuated in MP15-treated PAN rats. These data indicate that the mechanism for therapeutic effect of glucocorticoids on ROS-mediated renal injuries includes an enhancement of endogenous glomerular AOE activities, which attenuates lipid peroxidation of glomerular tissue.
 ...
PMID:Glucocorticoid activates glomerular antioxidant enzymes and protects glomeruli from oxidant injuries. 194 78

Changes in erythrocyte lipid peroxidation (measured as the concentration of malonyl dialdehyde), glutathione metabolism, antioxidant enzyme activities (glutathione peroxidase, catalase, and superoxide dismutase), the oxidized products of haemoglobin (Hb), and hydrogen peroxide (H2O2)-induced haemolysis were studied in six children with chronic renal failure treated with serial acetate and bicarbonate haemodialysis (HD). Ten age- and sex-matched children acted as controls. Malonyl dialdehyde levels were significantly higher and antioxidant enzyme activities lower in uraemic red blood cells (RBCs) compared with controls (P less than 0.05). Incubation of RBCs for 1 h with acetylphenylhydrazine induced a decrease in the concentration of reduced glutathione (P less than 0.001) and an increase in the level of oxidized products of Hb (P less than 0.001), but only in the uraemic patients. The H2O2 haemolysis test revealed a mild (n = 3) to increased (n = 3) haemolysis in the uraemic RBCs. Oxidative haemolysis is probably a multifactorial process in uraemic patients, and may be an important risk factor in HD therapy.
 ...
PMID:Erythrocyte defense mechanisms against free oxygen radicals in haemodialysed uraemic children. 203 30

Evidence suggests that the helminth antioxidant enzyme superoxide dismutase (SOD) may play a role in parasite's defense against the cellular immune mechanisms of the host. In order to investigate this for the human parasite Onchocerca volvulus, the enzyme activity was characterized, the release of SOD by the parasite was examined, and a complete cDNA encoding the O. volvulus SOD was identified. The SOD activity in adult O. volvulus was found to be 8.1 +/- 4.2 U/mg of protein. A Cu/Zn-containing enzyme was demonstrated by its sensitivity towards cyanide, azide, and hydrogen peroxide. Isoelectric focusing, combined with an enzyme activity assay, revealed two activities at pI 6.8 and 7.6, with both activities inhibited by KCN. Adult parasites, maintained in vitro, released SOD into the culture medium, which was detected by enzyme activity. In parallel, lactate production was measured to ensure the viability of the parasite. Oligonucleotides (based upon conserved sequences in the SOD genes of other organisms) and the polymerase chain reaction were used to identify a portion of the SOD gene from O. volvulus genomic DNA. A cDNA library was constructed in lambda unizapII and screened with the genomic polymerase chain reaction fragment. A complete cDNA encoding the Cu/Zn SOD was identified, and its nucleotide sequence was determined. Southern blot hybridization experiments indicated that the Cu/Zn SOD is encoded by a single-copy gene with at least one intron.
 ...
PMID:Characterization and molecular cloning of a Cu/Zn superoxide dismutase from the human parasite Onchocerca volvulus. 203 66

Washed red blood cells from preserved blood were used to elaborate a method suitable for the examination of red blood cell deformability and for the detection of changes in oxidative stress, i.e. for the determination of lipid peroxidation and antioxidant enzyme activity changes. The oxidative stress was induced by treatment of red blood cells with hydrogen peroxide.
 ...
PMID:Simple method for the measurement of antioxidants. 209 67

Thioredoxin reductase (TR) is a widely distributed flavoenzyme that provides reduced thioredoxin, a dithiol hydrogen donor for protein disulfide reduction and for the reduction of ribonucleotides to deoxyribonucleotides, the first unique step of DNA synthesis. Antitumor quinones were found to exhibit time- and concentration-dependent inhibition of purified rat liver TR that requires the presence of NADPH. Diaziquone initially shows competitive inhibition of the enzyme with 5,5'-dithiobis 2-nitrobenzoic acid as substrate with a Ki of 7.5 microM, which becomes non-competitive after 1 hour incubation with NADPH with a Ki of 0.5 microM. Doxorubicin shows non-competitive inhibition both initially and after 1 hr incubation with NADPH, with Ki values of 10 microM and 0.5 microM, respectively. Electron spin resonance spectroscopy showed the formation of semiquinone free radicals by TR incubated under anaerobic conditions with doxorubicin or diaziquone and NADPH. Redox cycling and formation of oxygen radicals does not play a major role in the inhibition of TR by antitumor quinones as shown by the minor effect on inhibition of removing O2, and the lack of effect of superoxide dismutase and catalase. Diaziquone causes time- and concentration-dependent inhibition of TR activity in intact A204 human rhabdomyosarcoma cells that is associated with growth inhibition. The results suggest that inhibition of TR by antitumor quinones could contribute to their growth inhibitory properties.
 ...
PMID:Inhibition of thioredoxin reductase (E.C. 1.6.4.5.) by antitumor quinones. 216 13

Efforts to reduce reperfusion injury have focused on exogenous therapies; however, endogenous attenuation of reperfusion injury can be induced by a single sublethal dose of endotoxin (ETX) prior to ischemia. The purposes of this study were to investigate (i) the early neutrophil-endothelial (PMN-EC) adherence, (ii) the associated myocardial oxidant stress, (iii) the relationship of oxidant stress to antioxidant enzyme activity, and (iv) the correlation of increased antioxidant enzyme activity to myocardial recovery following ischemia/reperfusion (I-R) injury at 36 hr. Rats were administered a sublethal dose (2% of LD50) of endotoxin (500 micrograms/kg, ip, Salmonella typhimurium). At 6 hr, myocardial neutrophil accumulation (histology), hydrogen peroxide (H2O2) levels, and myocardial tissue glutathione (glutathione and oxidized glutathione) levels were determined. At 24 hr myocardial tissue glutathione levels and catalase (CAT) activity were assayed. At 36 hr, myocardial tissue superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, and glucose-6-phosphate dehydrogenase (G-6-PD) were assayed. At 36 hr, hearts were subjected to a standard (20 min, global, 37 degrees C) ischemic insult followed by reperfusion. At 40 min of reperfusion, ventricular function was assessed (ventricular balloon; ventricular developed pressure +dP/dt, and -dP/dt).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Induction of endogenous tissue antioxidant enzyme activity attenuates myocardial reperfusion injury. 219 33


1 2 3 4 5 6 7 8 9 10 Next >>