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

Abnormalities in the cellular regulation and expression of antioxidant enzymes may have a role in mechanisms of central nervous system aging and neurodegeneration. We therefore examined, using isozyme-specific antibodies and immunohistochemistry, the localization of copper, zinc-superoxide dismutase and manganese-superoxide dismutase in the frontal and temporal neocortices and hippocampi of aged controls and individuals with Alzheimer's disease or Down's syndrome. Two different antibodies to copper, zinc-superoxide dismutase and one antibody to manganese-superoxide dismutase were evaluated by immunoblotting of homogenates of human brain before use in immunohistochemistry. The copper, zinc-superoxide dismutase antibodies recognized a single band of proteins at 16 kd. The manganese-superoxide dismutase antibody detected a single band of proteins at 25 kd. Immunohistochemically, copper, zinc-superoxide dismutase and manganese-superoxide dismutase immunoreactivities were localized predominantly to neocortical and hippocampal pyramidal neurons and scarcely seen in glial cells in controls. In Alzheimer's disease and Down's syndrome, the distributions and intensities of these two forms of superoxide dismutase immunoreactivities were different as compared with controls. Copper, zinc-superoxide dismutase was enriched in pyramidal neurons undergoing degeneration, whereas manganese-superoxide dismutase was more enriched in reactive astrocytes than in neurons. In senile plaques, copper, zinc-superoxide dismutase-positive globular structures were surrounded by astrocytes highly enriched in manganese-superoxide dismutase. By double label immunohistochemistry, some pyramidal neurons coexpressed superoxide dismutases and tau, and a few copper, zinc-superoxide dismutase-positive structures in senile plaques colocalized with tau. Amyloid cores, diffuse plaques, and microglia scarcely showed colocalization with superoxide dismutase-positive structures. The observed changes in the cellular localization of superoxide dismutases in neocortex and hippocampus in cases of Alzheimer's disease and Down's syndrome support a role for oxidative injury in neuronal degeneration and senile plaque formation. The differential localization of copper, zinc-superoxide dismutase and manganese-superoxide dismutase in cerebral sites of degeneration suggests that cellular responses to oxidative stress is antioxidant enzyme specific and cell type specific and that these two forms of superoxide dismutase may have different functions in antioxidant mechanisms.
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PMID:Localization of superoxide dismutases in Alzheimer's disease and Down's syndrome neocortex and hippocampus. 785 48

Analysis of activities of the antioxidant enzyme manganese superoxide dismutase in human renal cell carcinomas often showed greatly altered enzyme levels (either elevated or depressed) compared to the cell of origin, the kidney proximal tubule. In order to better understand the variability observed, immunogold studies were performed on human renal cell carcinomas using a polyclonal antibody to human kidney manganese superoxide dismutase. For comparison, studies were also performed using antibodies to other antioxidant enzymes. For histologic studies, renal cell carcinomas were subclassified on the basis of light microscopy and ultrastructural analysis into clear cell, granular cell, or mixed clear and granular cell variants. In all three types of tumor, immunogold studies showed little staining using antibodies to copper, zinc superoxide dismutase or glutathione-dependent enzymes. However, intensity of labeling for manganese superoxide dismutase and catalase depended on the cell type(s) in the tumor. Clear cell variants demonstrated trace staining for manganese superoxide dismutase and catalase, while granular cell variants exhibited heavy staining for both of these enzymes. Mixed types of tumors showed clear cells with trace staining for all antioxidant enzymes examined, while granular cells again showed intense labeling for manganese superoxide dismutase and catalase. Using normal kidney proximal tubule as a comparison, immunogold ultrastructural analysis using antibody to manganese superoxide dismutase demonstrated infrequent small lightly labeled mitochondria in clear cell variants, while granular cell variants exhibited numerous medium-sized heavily labeled mitochondria. These data suggest that: 1) the variability in activity values for manganese superoxide dismutase may be due to heterogeneity of cell types in these tumors and 2) manganese superoxide dismutase immunoreactive protein was elevated in granular cells both because of an increase in number of mitochondria and because the labeling density in mitochondria was increased compared to mitochondria in clear cell types or in normal proximal tubular cells.
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PMID:Immunogold analysis of antioxidant enzymes in human renal cell carcinoma. 818 Jul 77

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.
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PMID:Expression of antioxidant enzymes in rat kidney during ischemia-reperfusion injury. 828 74

The essential nutrients zinc (Zn) and selenium (Se) provide an antioxidant function to animal cells by very different mechanisms. Se is an integral part of Se-dependent glutathione peroxidases, a group of water-soluble enzymes that catalyze the destruction of water-soluble and, in some cases, membrane-bound hydroperoxides. In dietary Se deficiency, Se-dependent glutathione peroxidase activities are decreased; at Se intakes above that which is required for optimal growth, there is a slight to moderate increase in Se-dependent glutathione peroxidase activities. Because of the enzymatic nature of the major role of Se as an antioxidant, Se can be categorized as having a general antioxidant function, controlling peroxide levels in cells by degrading hydroperoxides. On the other hand, Zn functions as an antioxidant only at specific sites, and is not a required cofactor for an antioxidant enzyme. Although Zn plays a structural role in the enzyme Cu, Zn superoxide dismutase, the activity of this enzyme is not decreased in Zn deficiency and its activity is usually depressed at high Zn intakes. Zn may function as a site-specific antioxidant by two mechanisms. Firstly, it competes with Fe and Cu for binding to cell membranes and some proteins, displacing these redox-active metals and making them more available for binding to ferritin and metallothionein, respectively. Secondly, Zn binds the sulfhydryl groups in proteins, protecting them from oxidation. Zn status does not directly control tissue peroxide levels but can protect specific molecules against oxidative and peroxidative damage.
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PMID:Zinc and selenium, site-specific versus general antioxidation. 831 37

Normal embryonal mouse liver cells in culture were shown to undergo spontaneous transformation during prolonged subculture. The spontaneously transformed cells lost their anchorage dependence, as measured by a soft agar assay, and gave rise to tumors in nude mice. Accompanying this transformation, the antioxidant enzymes, copper- and zinc-containing superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), catalase (CAT) and glutathione reductase, decreased significantly in activity; the decline in enzymatic activity of CuZnSOD, MnSOD and CAT was due to a decline in the levels of immunoreactive protein. These spontaneously transformed high passage in vitro liver cells appeared similar in morphology, antioxidant enzyme activity and tumorigenicity to their counterparts transformed by N-methyl-N-nitro-N-nitrosoguanidine and Simian virus 40. These data provide experimental evidence that changes in antioxidant enzymes are associated with spontaneous in vitro cellular transformation of mouse embryonal liver cells.
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PMID:Lowered antioxidant enzymes in spontaneously transformed embryonic mouse liver cells in culture. 833 Mar 64

This study examined whether brief repeated myocardial ischemia altered free radical generating and scavenging activity in a dog model. In dogs preconditioned with four 5-min left anterior descending coronary artery (LAD) occlusions and reperfusions, we examined transcardiac changes in both the function of neutrophils, cells which are major free radical generators, and in myocardial antioxidant enzyme activity, as an indication of free radical scavenging. Neutrophil function was assessed by determining luminol-enhanced whole blood chemiluminescence (CL) induced by zymosan. Blood was taken simultaneously from the carotid artery and the cardiac vein running along the occluded LAD. Preconditioning with sublethal ischemia significantly reduced whole blood CL in the cardiac vein compared with the carotid artery after the first and fourth 5-min reperfusions, while there was no difference in neutrophil count between these sampling sites. Immediately after brief repeated ischemia and reperfusion, manganese-superoxide dismutase (SOD) activity was significantly enhanced, and glutathione reductase activity was markedly reduced in the ischemic, compared with the non-ischemic, myocardium. There were no differences in the myocardial activities of copper, zinc-SOD, glutathione peroxidase, and glutathione S-transferase between the ischemic and non-ischemic regions. Also, no difference was observed between the reduced myocardial glutathione levels in these regions, although the oxidized glutathione level was significantly higher in the ischemic regions of the subepicardial and subendocardial areas. We demonstrated that brief repeated ischemia affects free radical generating and scavenging systems in the ischemic myocardium.
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PMID:Brief myocardial ischemia affects free radical generating and scavenging systems in dogs. 840 20

The biochemical maturation of the lung in late gestation and in the young animal is regulated by glucocorticoids. The present study was aimed at dissociating the different glucocorticoid receptor sites involved in these regulatory functions. The obese Zucker rat was selected as a model for this study as it exhibits hypersensitivity to glucocorticoid hormone action by virtue of its elevated receptor numbers and activity. Two synthetic steroid analogues were administered to obese animals; RU28362, a specific type II receptor agonist, and the type II antagonist RU486. RU28362 promoted a strong catabolic effect, which was associated with reduced food intake and the abolition of growth in the rats. The agonist, RU28362, attenuated developmental increases in antioxidant enzyme activities, and altered the growth of the tissue. At the age studied, development of the lung phosphatidylcholine (PC) system was almost complete, but RU28362 increased disaturated PC 16:0/16:0 concentrations by almost 2-fold, and altered the molecular composition of total pulmonary PC. RU486 attenuated the growth of the rats and reduced their food intake. Treatment with the type II antagonist attenuated lung growth and increased the activities of pulmonary copper zinc (Cu/Zn) and manganese (Mn) superoxide dismutases. RU486 had no effect on lung PC concentrations and molecular composition. The data suggest a role for type I glucocorticoid receptors in the regulation of the antioxidant enzyme system in the lung, as type II antagonism will channel endogenous glucocorticoid binding to the type I site. Type II receptor binding would appear to play a role in regulating the lung PC content.
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PMID:Effects of the glucocorticoid agonist, RU28362, and the antagonist RU486 on lung phosphatidylcholine and antioxidant enzyme development in the genetically obese Zucker rat. 844 53

Immunolocalization studies of hamster kidney development were performed using polyclonal antibodies to antioxidant enzymes, including antibodies to copper, zinc and manganese superoxide dismutases, catalase, glutathione peroxidase and glutathione S-transferases and their subunits. Antibodies to extracellular matrix proteins were also studied to determine the temporal sequence between expression of immunoreactive protein for basement membrane proteins, which serve as markers of embryonic induction of nephron development, and antioxidant enzyme expression in kidney development. Immunoreactive proteins for antioxidant enzymes were not detectable in the developing kidney until after extracellular matrix proteins had been deposited. However, immunoreactive proteins for the antioxidant enzymes copper, zinc and manganese superoxide dismutases, catalase, and alpha class glutathione S-transferase Ya subunit were detected in renal tubules before birth. mu class glutathione S-transferase subunits Yb1 and Yb2 stained transitional epithelium at high levels before birth. Our results indicate: (1) each type of kidney cell has a unique antioxidant enzyme profile, (2) antioxidant enzymes are expressed in different types of cell at different times during development, but antioxidant enzyme immunoreactive protein was not present until after immunoreactive proteins for extracellular matrix molecules were detected, and (3) certain antioxidant enzymes are present before birth, indicating that high oxygen tension present at birth is not crucial for induction of immunoreactive protein.
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PMID:Immunohistochemical localization of antioxidant enzymes during hamster kidney development. 855 Mar 76

For this article we investigated the role of three blood antioxidant enzyme activities and total antioxidant status (TAS) as biological markers of oxidative stress in workers exposed to mercury (Hg(o)) vapors. Twenty-two female workers took part in the study. The examination included a questionnaire on age, educational level, occupational history, actual health status, previous accidents and diseases, smoking and dietary habits, and alcohol consumption. Blood and urine sampling for biological analyses completed this examination. The workers were classified into three subgroups according to their creatinine-corrected Hg concentration in urine. Blood antioxidant enzyme activities and TAS were compared between groups with nonparametric distribution-free methods. A significant difference existed in catalase activity and a slight, but not significant, difference existed in Cu2+/Zn2+ superoxide dismutase (Cu2+/Zn2+ SOD) activity between the three groups. No differences were observed in either the glutathione peroxidase activity or the TAS between these groups. Catalase and Cu2+/Zn2+ SOD activities were increased in the groups of workers with higher creatinine-corrected urinary Hg concentrations when compared with the group of lower creatinine-corrected urinary Hg concentrations. Catalase activity was positively correlated with the creatinine-corrected concentration of Hg in urine, and Cu2+/Zn2+ SOD activity was slightly correlated with the creatinine-corrected concentration of Hg in urine. The role of erythrocyte catalase and Cu2+/Zn2+ SOD activities we have measured is in agreement with the hypothesis of the involvement of reactive oxygen species production as an important event in chronic exposure to Hg(o) vapors in humans. In spite of the small size of the sample, these results indicate that erythrocyte catalase and Cu2+/Zn2+ SOD activities could be considered as markers of biological effect in workers exposed to Hg(o) vapors.
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PMID:Catalase and superoxide dismutase activities as biomarkers of oxidative stress in workers exposed to mercury vapors. 864 19

New atherosclerosis causative factors and preventive modalities have been identified. Atherogenic factors include lipid oxidation products, such as cholesterol oxidation products, malonaldehyde and other aldehydes; trans-fatty acids; some saturated fatty acids (lauric, myristic and possibly palmitic acids); and myristic acid plus cholesterol. Lipid oxidation products are well suited to induce arterial damage, based on their known cytotoxic effects; evidence also indicates the possibility of plaque promotion and stimulation of thrombogenesis. Anti-atherogenic factors include antioxidants, fish oils and other polyunsaturates (if protected from oxidation), fibre and trace minerals such as copper, manganese, selenium and zinc. Iron is unique, being considered as both a potential promoter of atherosclerosis (component of ferritin, conceivably inducing lipid oxidation) and a possible anti-atherogenic component (of antioxidant enzyme catalase). It is apparent that an entire new series of research challenges has been uncovered.
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PMID:Atherogenic and anti-atherogenic factors in the human diet. 866 Apr


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