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)

In earlier studies we have shown that the activity of the antioxidant enzyme glutathione peroxidase is regulated by oxygen tension in cultured tetralogy of Fallot (TOF) ventricular myocytes and in the ventricles of TOF patients having corrective cardiac surgery. The present study was undertaken to determine the mechanism of this regulation. Northern and slot blot analysis was performed using RNA isolated from TOF myocytes cultured at oxygen tensions of 150 and 40 mmHg for 3, 7, 14, 21, and 28 days. As was found for enzyme activities, glutathione peroxidase mRNA levels were lower in the cells cultured at a pO2 of 40 mmHg than at 150 mmHg and could be elevated with an increase in oxygen tension. These results were standardized against house-keeping gene hexosaminidase B which showed no difference in mRNA levels between the two oxygen tensions throughout the time course. Nuclear run-off assays indicated that glutathione peroxidase was regulated by oxygen tension at the transcriptional level, while hexosaminidase B and total mRNA synthesis levels remained unchanged.
J Mol Cell Cardiol 1992 Apr
PMID:The regulation of glutathione peroxidase gene expression by oxygen tension in cultured human cardiomyocytes. 153 67

The activities of superoxide dismutase (SOD; EC 1.15.1.1) and glutathione peroxidase (GSHPx; EC 1.11.1.9), the enzymes that metabolize the superoxide anion and hydrogen peroxide, respectively, were measured in serum from healthy subjects and patients with Parkinson's disease (PD). The activities of SOD and GSHPx in patients with PD were higher than those in normal healthy individuals. These results suggest that the increased activities of these enzymes could be due to oxidative stress in the initial stages of this disease.
Mol Cell Biochem 1992 Mar 25
PMID:Serum antioxidant enzyme activity in Parkinson's disease. 158 6

The effect of dichlorvos exposure (5 mg kg-1 body wt, ip) on lipid peroxidation and antioxidant defense system in different regions of the rat central nervous system was studied. In the present paper an inhibition of acetylcholinesterase activity was used as an index of dichlorvos neurotoxicity. We observed significant increases in the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase which were accompanied by a decrease in the values of lipid peroxidation. Dichlorvos exposure also resulted in a significant decrease in glutathione peroxidase activity. The decreased levels of both reduced and oxidized glutathione as observed on dichlorvos exposure affected the GSH/GSSG ratio. These results indicate that the enzymes SOD and catalase may enhance the disposal of potentially toxic radicals. Furthermore, the decrease in GSH levels may be a mechanism for the detoxification of dichlorvos in the brain.
Exp Mol Pathol 1992 Apr
PMID:Neurotoxicity of dichlorvos: effect on antioxidant defense system in the rat central nervous system. 158 40

Incubation of freshly isolated rat liver mitochondria in the presence of oxygen free radical generating hypoxanthine-xanthine oxidase system led to swelling of mitochondria as measured by the change in optical density, which was reversed by the addition of superoxide dismutase. O2- in the presence of CaCl2 enhanced the peroxidative decomposition of mitochondrial membrane lipids along with swelling of the organelle. Free radical generation led to enhancement of monoamine oxidase activity while glutathione peroxidase and cytochrome c oxidase were inhibited. Tert-butyl hydroperoxide (t-BHP) caused mitochondrial swelling through oxidative stress. Incorporation of ruthenium red, which is a Ca2+ transport blocker, during assay abolished peroxidative membrane damage and swelling. Dithiothreitol (DTT) accorded protection against t-BHP induced mitochondrial swelling. The above in vitro data suggest a possible interrelationship of active oxygen species, membrane damage and calcium dynamics.
Mol Cell Biochem 1992 Apr
PMID:Interrelation of active oxygen species, membrane damage and altered calcium functions. 158 33

Rats were subjected to bilateral carotid artery occlusion for 30 min, followed by reperfusion for varying time periods. The concentration of reduced and oxidized glutathione, glutathione peroxidase and glutathione reductase were determined in whole brain after varying periods of reperfusion. Lipid peroxidation was also assessed by determining the levels of malondialdehyde (MDA) in the brain. Reperfusion for 1 hr following bilateral carotid artery occlusion resulted in significant decrease in total glutathione (GSH) concentration along with small but significant increase in oxidized glutathione (GSSG) levels. After 4 hr of reperfusion, GSH levels recovered, although GSSG levels remained elevated up to 12 hr of reperfusion. Increase in malondialdehyde levels was also detected in the brain up to 12 hr of reperfusion. Glutathione reductase activity remained significantly low up to 144 hr of reperfusion, while glutathione peroxidase activity remained unaffected. These results demonstrate that oxidative stress is generated in the brain during reperfusion following partial ischemia due to bilateral carotid artery occlusion.
Mol Cell Biochem 1992 Apr
PMID:Glutathione homeostasis in brain during reperfusion following bilateral carotid artery occlusion in the rat. 158 35

Ascorbic acid (AH2) is a potential scavenger of superoxide radical and singlet oxygen. In the guinea pig, marginal AH2 deficiency results in intracellular oxidative damage in the cardiac tissue as evidenced by lipid peroxidation, formation of fluorescent pigment and loss of structural integrity of the microsomal membranes. The oxidative damage does not occur due to lack of enzymatic scavengers of reactive oxygen species such as superoxide dismutase, catalase and glutathione peroxidase. Also, glutathione transferase activity is not decreased in AH2 deficiency. Lipid peroxidation, fluorescent pigment formation and protein modification disappear after AH2 therapy. These results, if extra-polated to human beings, would indicate that chronic subclinical AH2 deficiency may result in progressive oxidative damage which in the long run may lead to permanent degenerative diseases in the heart.
Mol Cell Biochem 1992 Apr
PMID:Protective role of ascorbic acid against lipid peroxidation and myocardial injury. 158 41

To protect against reactive oxygen species, prokaryotic and eukaryotic cells have developed an antioxidant defence mechanism where O2- is converted to H2O2 by superoxide dismutase (Sod), and in a second step, H2O2 is converted to H2O by catalase (Cat) and/or glutathione peroxidase (Gpx). If Sod levels are increased without a concomitant Gpx increase, then the intermediate H2O2 accumulates. This intermediate could undergo the Fenton's reaction, generating hydroxyl radicals which may lead to lipid peroxidation in cells. In this study, we investigate the expression of Sod1, Gpx1 and susceptibility to lipid peroxidation during the aging process in mouse brains. We demonstrate that the mRNA levels and enzyme activity of Sod1 are higher in brains from adult mice compared to neonatal mice. Furthermore, we show that a linear increase in Sod1 mRNA and enzyme activity occurs with aging (1-100 weeks). On the contrary, we find that the mRNA and enzyme activity for Gpx1 does not increase with aging in mouse brains. In addition, our results demonstrate that the susceptibility of murine brains to lipid peroxidation increases with aging. The data in this study are consistent with the notion that reactive oxygen species may contribute to the aging process in mammalian brains. These results are discussed in relation to the normal aging process in mammals, and to the premature aging and mental retardation in Down syndrome.
Brain Res Mol Brain Res 1992 Apr
PMID:Cu/Zn superoxide dismutase mRNA and enzyme activity, and susceptibility to lipid peroxidation, increases with aging in murine brains. 159 44

The role of different antioxidant pathways in cultured rat pleural mesothelial cells was studied by exposing the cells to various hydrogen peroxide (H2O2) concentrations and by measuring H2O2 cell cytotoxicity and the capacity of the cells to scavenge H2O2. The antioxidant enzymes, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and catalase were analyzed biochemically. Catalase and CuZn superoxide dismutase were localized by immunocytochemistry. To enable investigation of the glutathione redox cycle and catalase pathways, glutathione reductase was inactivated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and catalase was inactivated with aminotriazole. When the cells were exposed to a low, sublethal (0.030 mM) H2O2 concentration, glutathione reductase but not catalase inactivation resulted in a decreased capacity to remove H2O2 from the extracellular medium. When the cells were exposed to a high (0.25 mM) H2O2 concentration, H2O2-scavenging capacity decreased remarkably when catalase was inactivated. When the cells were exposed to 0.1 to 0.5 mM H2O2, cell cytotoxicity (lactate dehydrogenase release) increased significantly if glutathione reductase was inactivated; catalase inactivation resulted in a significant cytotoxicity only at high (greater than or equal to 0.25 mM) H2O2 concentrations. Immunocytochemical studies showed that the cells, both in situ and in vitro, contained low amounts of catalase. This suggests that the results of the catalase-inhibition studies are probably not due to a change in the characteristics of the cells in culture. 3-Aminobenzamide is a compound that is known to prevent NAD depletion through inhibition of poly(ADP-ribose) polymerase during oxidant stress. When intact cells were treated with different antioxidants and exposed to 0.5 mM H2O2, both catalase and 3-aminobenzamide protected the cells completely.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Jul
PMID:Antioxidant defense mechanisms in cultured pleural mesothelial cells. 162 38

To explore the level of regulation of the expression of the major antioxidant enzymes in response to hyperoxia, we exposed human umbilical vein endothelial cells to 95% O2 for 3 and 5 days and measured (1) the steady-state mRNA levels, (2) the activities, and (3) the immunoreactive content of CuZn and Mn superoxide dismutases (SOD), catalase (CAT), and glutathione peroxidase (GP). We found that a 3-day exposure to 95% O2 caused (1) an increase in CuZnSOD mRNA (by 41%), CAT mRNA (by 26%), and GP mRNA (by 173%); (2) an increase in CuZnSOD activity (by 30%), a decrease in CAT activity (by 37%), and an increase in GP activity (by 60%); and (3) an increase in CuZnSOD immunodetectable protein (by 26%) and a loss in CAT immunoreactive protein (by 27%). After a 5-day exposure to 95% O2, there was (1) a 93% increase in CuZnSOD mRNA, a 71% increase in CAT mRNA, and a 127% increase in GP mRNA; (2) a 56% increase in CuZnSOD activity, a 70% decrease in CAT activity, and an 89% increase in GP activity; and (3) a 35% increase in CuZnSOD immunoreactive protein and a 55% loss in CAT immunoreactive protein. There was no change in the steady-state MnSOD mRNA level after 3 days in 95% O2, but a 100% increase was observed on day 5 of oxygen exposure. MnSOD activity was unchanged in cells exposed to hyperoxia for 3 and 5 days. These data suggest that, in human umbilical vein endothelial cells, the regulation of antioxidant enzymes expression in response to O2 is complex and exerted at different levels.
Am J Respir Cell Mol Biol 1992 Jan
PMID:Response of human endothelial cell antioxidant enzymes to hyperoxia. 172 89

Superoxide dismutase (SOD) was purified to apparent homogeneity from Dirofilaria immitis, the causative agent of Dog Heartworm disease which is prevalent in the Southeastern United States. The enzyme has a molecular weight of 18,000 under denaturing conditions with an isoelectric point of 5.6. Both values are similar to those found for previously purified helminth SODs. The amino acid analysis shows greater similarity with mammalian SODs than with the published Schistosoma mansoni SOD, probably because the S. mansoni enzyme appears to be an extracellular, not a cytosolic, SOD. Although SOD activity is easily detected in D. immitis homogenates, the hydrogen peroxide scavenging activities of catalase and glutathione peroxidase were below the limits of our assay. This suggests that D. immitis primary defense against oxidants may be SOD. We feel that this line of research may provide valuable insights into a vulnerable area of D. immitis that may be a good target for drug therapy.
Mol Biochem Parasitol 1991 Dec
PMID:Dirofilaria immitis superoxide dismutase: purification and characterization. 177 68


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