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)

The effects of aging on myocardial antioxidant enzyme activity, lipid peroxidation, and other related biochemical properties were investigated in male Wistar-Furth rats at 4, 26, and 31 mo of age at rest and after an acute exercise bout. The results showed that resting heart cytosolic superoxide dismutase (CuZn SOD) activity was significantly decreased in the heart with aging (66 +/- 6.5 U/mg protein at 4 mo vs. 49 +/- 3.8 U/mg protein at 31 mo) and was elevated in all age groups after exercise. Mitochondrial Mn SOD activity was almost doubled in both 26- and 31-mo-old rats compared with that at 4 mo. Myocardial catalase and cytosolic glutathione peroxidase (GPX) activities were significantly decreased with age, whereas mitochondrial GPX was 29% higher (P less than 0.05) in 31- than 4-mo-old rats. Glutathione S-transferase activity in the heart also declined with age (P less than 0.05 at 31 mo). Malondialdehyde contents in both heart homogenate and mitochondria were significantly increased at old age. Activity of several enzymes related to myocardial energy production, e.g., citrate synthase, malate dehydrogenase, and lactate dehydrogenase, as well as myocardial protein content showed an age-related decline. These data indicate that myocardial antioxidant capacity is weakened during aging and that the compensatory increases of mitochondrial SOD and GPX may be an important mechanism in coping with free radical damage in senescent heart. Findings in the present investigation seem to support the free radical theory of aging.
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PMID:Myocardial aging: antioxidant enzyme systems and related biochemical properties. 187 97

We have previously identified and characterized GSHPx-GI, which is a cellular selenium-dependent glutathione peroxidase (GSHPx) distinct from the classic GSHPx-1 and phospholipid hydroperoxide glutathione peroxidase (PHGPX). We have determined the level of GSHPx-GI mRNA expression in the rat gastrointestinal tract from esophagus to colon. Although GSHPx-GI mRNA is readily detectable throughout the GI tract, the highest level is detected in the ileum and cecum. We have also determined the levels of GSHPx-GI mRNA expression and several antioxidant enzyme activities along the villus-to-crypt axis in the rat small intestine by cell fractionation. GSHPx-GI mRNA is present at a similar level in all of the epithelial fractions, whereas GSHPx-1 mRNA is detectable only in the remnant. This suggests that GSHPx-GI is the major cellular tetrameric GSHPx expressed in intestinal epithelium, and the expression of GSHPx-GI in the GI tract is not likely regulated differentially through maturation of epithelial cells. In terms of enzymatic activity, although we detected lower glutathione S-transferase activity in the crypt epithelium, there was a marginal increase of PHGPX activity, a twofold increase of GSHPx activity, and a three- to fivefold increase of catalase activity in the crypt relative to the distal villus. Thus, the crypt epithelial cells may be better protected from peroxidative damage.
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PMID:The expression of an intestinal form of glutathione peroxidase (GSHPx-GI) in rat intestinal epithelium. 748 90

In eukaryotes, incorporation of selenocysteine into the polypeptide chain at a UGA codon requires a unique sequence motif, or "selenium translation element" (STE), located in the 3'-untranslated region of the mRNA. The present study examines structure-function relationships of conserved sequence elements and of the putative stem-loop secondary structure in the STE of human GPX1 mRNA, which encodes the important antioxidant enzyme cellular glutathione peroxidase (EC 1.11.1.9). Deletion of the basal stem, upper stem, or apical loop of the stem-loop structure eliminated the ability of the STE to direct selenocysteine incorporation at the UGA codon of an epitope-tagged GPX1 reporter construct transfected into COS1 cells. However, mutations that change the primary nucleotide sequence of nonconserved portions of the stem-loop, but preserve its overall secondary structure, by inversion of apical loop sequences or exchange of 5' and 3' sides of stem segments, had little or no effect on selenocysteine incorporation. Effects of single- and double-nucleotide substitutions in three short, highly conserved elements in the GPX1 STE depended in large part on their computer-predicted perturbation of the stem-loop and its midstem bulge. Only in the conserved "AAA" apical loop sequence did mutations show major effects on function without predicted changes in secondary structure. Our results demonstrate the critical role of the three short, highly conserved sequences. However, outside of these elements, the function of the human GPX1 STE appears to depend strongly on the stem-loop secondary structure.
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PMID:Structure and function of the selenium translation element in the 3'-untranslated region of human cellular glutathione peroxidase mRNA. 748 13

The testis is known to be highly sensitive to a number of physical stresses. Previous investigations suggest that oxidative stress may be an important mediator of testicular injury. The ability of the testis to manage oxidative stress may be limited by enzymatic clearance of reactive oxygen species (ROS). To evaluate the ability of the testis to withstand the common pathologic conditions of cryptorchidism and obstruction, we measured mRNA levels of testicular antioxidant enzymes. Prepubertal rats were rendered unilaterally cryptorchid and 40 days after the procedure, cryptorchid, contralateral and control (sham) testes were harvested for RNA extraction. Adult rats were subjected to unilateral efferent duct ligation and the obstructed testes harvested 1 to 28 days after the procedure. Antioxidant enzyme mRNA expression was assessed by Northern blot analysis using 32P-labeled DNA probes for classical cellular glutathione peroxidase (GSHPx), phospholipid hydroperoxide glutathione peroxidase (PHGPX), Cu/Zn superoxide dismutase (SOD) and catalase. In both cryptorchid and contralateral testes, the germ cell-specific 0.9 kb SOD and PHGPX mRNA transcript levels were significantly decreased compared to control testes (p < 0.05). Similarly, after efferent duct ligation, the 0.9 kb SOD and PHGPX mRNA transcript levels also decreased compared to control testes (p < 0.05). These findings suggest that the overall decline in testicular mRNA transcript levels after efferent duct ligation and cryptorchidism is primarily due to germ cell depletion. Reduced levels of antioxidant enzyme mRNAs in cryptorchid testes have been documented. Further experiments may elucidate the role of increased oxidative stress associated with decreased antioxidants in cryptorchidism. It remains to be determined whether oxidative stress has a causative role in the abnormal spermatogenesis and tumorigenesis associated with cryptorchidism.
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PMID:Cu/Zn superoxide dismutase, catalase and glutathione peroxidase mRNA expression in the rat testis after surgical cryptorchidism and efferent duct ligation. 922 87

Reactive oxygen species (ROS) have been implicated in the pathogenesis of many clinical disorders such as adult respiratory distress syndrome, ischemia-reperfusion injury, atherosclerosis, neurodegenerative diseases, and cancer. Genetically engineered animal models have been used as a tool for understanding the function of various antioxidant enzymes in cellular defense mechanisms against various types of oxidant tissue injury. Transgenic mice overexpressing three isoforms of superoxide dismutase, catalase, and the cellular glutathione peroxidase (GSHPx-1) in various tissues show an increased tolerance to ischemia-reperfusion heart and brain injury, hyperoxia, cold-induced brain edema, adriamycin, and paraquat toxicity. These results have provided for the first time direct evidence demonstrating the importance of each of these antioxidant enzymes in protecting the animals against the injury resulting from these insults, as well as the effect of an enhanced level of antioxidant in ameliorating the oxidant tissue injury. To evaluate further the nature of these enzymes in antioxidant defense, gene knockout mice deficient in copper-zinc superoxide dismutase (CuZnSOD) and GSHPx-1 have also been generated in our laboratory. These mice developed normally and showed no marked pathologic changes under normal physiologic conditions. In addition, a deficiency in these genes had no effects on animal survival under hyperoxida. However, these knockout mice exhibited a pronounced susceptibility to paraquat toxicity and myocardial ischemia-reperfusion injury. Furthermore, female mice lacking CuZnSOD also displayed a marked increase in postimplantation embryonic lethality. These animals should provide a useful model for uncovering the identity of ROS that participate in the pathogenesis of various clinical disorders and for defining the role of each antioxidant enzyme in cellular defense against oxidant-mediated tissue injury.
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PMID:The nature of antioxidant defense mechanisms: a lesson from transgenic studies. 978 1

There is increasing evidence that free radical scavengers play an important role in the aging process and the control of cellular growth. We purified a free radical scavenging protein, the water-soluble protein (WSP) from broad beans (Vicia faba). In this study, we examined the effect of WSP on cellular growth and in vitro life span in old human fetal lung fibroblasts (WI-38 and PDL 37-40, 78-84% of the maximum life span). Since WSP increased the cellular growth, we also examined the effect of WSP (1.25-5 microg/ml) on cytosolic antioxidant enzyme activities in the old cells treated or not with tert-butyl hydroperoxide (BHP) to elucidate the mechanisms of cell proliferation in the old cells. The cellular growth of old fibroblasts was greatly increased by WSP. In 1.25 and 2.5 microg/ml of WSP, the cell proliferation increased by 32 and 35%, respectively, as compared with controls. The maximum population doubling levels of the cells did not increase. In the cells incubated with BHP, the cytosolic superoxide dismutase activity was returned to its control value by WSP treatment (1.25-5 microg/ml). The cytosolic glutathione peroxidase activity progressively increased with increasing concentrations of WSP. On the other hand, the cytosolic superoxide dismutase activity after 1.25- and 2.5- microg/ml WSP treatment without BHP was increased by 189 and 144%, respectively. Similarly, the cytosolic glutathione peroxidase activity was increased by 67 and 53%, respectively. These results suggest that cytosolic antioxidant activities in old cells can be modulated by WSP treatment. We concluded that there was a correlation between the optimum WSP concentrations for the increase of cellular growth and the WSP concentrations required to exhibit these maximum enzyme activities.
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PMID:Increase of the cellular growth of old human diploid fibroblasts by radical scavenger: water-soluble protein from broad beans. 993 28

The methanolic extract from broad beans (MEBB), which is comprised of phenolic compounds, has free-radical scavenging activity. The effects of MEBB on cytosolic antioxidant enzymes and cell proliferation were examined in cultures of old (78-84% life-span completed) WI-38 human diploid fibroblasts. Because catechin is polyphenol and has radical scavenging activity, it was used as the control in experiments. We observed that MEBB increased cellular growth when added to the cell culture. In MEBB at 40 and 120 micrograms/mL, the cell proliferation increased by 14 and 27%, respectively, as compared to the control. In catechin, cell proliferation increased as well. Regarding cytosolic glutathione peroxidase (GSH-Px) activity, treatment of old cells with MEBB at 40 and 120 micrograms/mL resulted in decreases as compared to the control. In contrast, catechin showed no similarities to the modification of GSH-Px activity. Cytosolic SOD activity was increased by treatment with 40 micrograms/mL MEBB, and the activity showed a gradual decrease with increased MEBB concentrations. A similar trend occurred in the cells treated with catechin (4-20 microM). These results suggest that cytosolic antioxidant enzyme activities in old cells may be modulated by MEBB treatment. We conclude that there may be a relation between the optimum MEBB concentration for the increase of cellular growth and the MEBB concentration required to exhibit a decrease in GSH-Px activity.
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PMID:Increase of the cellular growth of old human diploid fibroblasts by radical scavenger: methanolic extract of broad beans. 1052 46

Respiratory function of mitochondria is compromised in aging human tissues and severely impaired in the patients with mitochondrial disease. A wide spectrum of mitochondrial DNA (mtDNA) mutations has been established to associate with mitochondrial diseases. Some of these mtDNA mutations also occur in various human tissues in an age-dependent manner. These mtDNA mutations cause defects in the respiratory chain due to impairment of the gene expression and structure of respiratory chain polypeptides that are encoded by the mitochondrial genome. Since defective mitochondria generate more reactive oxygen species (ROS) such as O2- and H2O2 via electron leak, we hypothesized that oxidative stress is a contributory factor for aging and mitochondrial disease. This hypothesis has been supported by the findings that oxidative stress and oxidative damage in tissues and culture cells are increased in elderly subjects and patients with mitochondrial diseases. Another line of supporting evidence is our recent finding that the enzyme activities of Cu,Zn-SOD, catalase and glutathione peroxidase (GPx) decrease with age in skin fibroblasts. By contrast, Mn-SOD activity increases up to 65 years of age and then slightly declines thereafter. On the other hand, we observed that the RNA, protein and activity levels of Mn-SOD are increased two- to three-fold in skin fibroblasts of the patients with CPEO syndrome but are dramatically decreased in patients with MELAS or MERRF syndrome. However, the other antioxidant enzymes did not change in the same manner. The imbalance in the expression of these antioxidant enzymes indicates that the production of ROS is in excess of their removal, which in turn may elicit an elevation of oxidative stress in the fibroblasts. Indeed, it was found that intracellular levels of H2O2 and oxidative damage to DNA and lipids in skin fibroblasts from elderly subjects or patients with mitochondrial diseases are significantly increased as compared to those of age-matched controls. Furthermore, Mn-SOD or GPx-1 gene knockout mice were found to display neurological disorders and enhanced oxidative damage similar to those observed in the patients with mitochondrial disease. These observations are reviewed in this article to support that oxidative stress elicited by defective respiratory function and impaired antioxidant enzyme system plays a key role in the pathophysiology of mitochondrial disease and human aging.
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PMID:Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system. 1140 14

Reactive oxygen species (ROS) and oxidative stress have been implicated in cochlear injury following loud noise and ototoxins. Genetic mutations that impair antioxidant defenses would be expected to increase cochlear injury following acute insults and to contribute to cumulative injury that presents as age-related hearing loss. We examined whether genetically based deficiency of cellular glutathione peroxidase, a major antioxidant enzyme, increases noise-induced hearing loss in mice. Two-month-old "knockout" mice with a targeted inactivating mutation of the gene coding for glutathione peroxidase (Gpx1) and wild type controls were exposed to broadband noise for one hour at 110 dB SPL. Auditory brainstem response (ABR) thresholds at test frequencies ranging from 5 to 40 kHz were obtained two and four weeks after exposure to determine the stable permanent component of the hearing loss. Depending on test frequency, (compared with controls) Gpx1 knockout mice showed up to 16 dB higher ABR thresholds prior to noise exposure, and up to 15 dB greater noise-induced hearing loss, compared with normal control. Within the cochlear base, there was also a significant contribution of the knockout to inner and outer hair cell loss, as well as nerve fiber loss. Our results support a link between genetic impairment of antioxidant defenses, vulnerability of the cochlea injury, and cochlear degeneration. Such impairment produces characteristics expected of some mutations associated with age-related hearing loss and offers one possible mechanism for their action.
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PMID:Targeted mutation of the gene for cellular glutathione peroxidase (Gpx1) increases noise-induced hearing loss in mice. 1154 30

Homocyst(e)ine (Hcy) inhibits the expression of the antioxidant enzyme cellular glutathione peroxidase (GPx-1) in vitro and in vivo, which can lead to an increase in reactive oxygen species that inactivate NO and promote endothelial dysfunction. In this study, we tested the hypothesis that overexpression of GPx-1 can restore the normal endothelial phenotype in hyperhomocyst(e)inemic states. Heterozygous cystathionine beta-synthase-deficient (CBS((-/+))) mice and their wild-type littermates (CBS((+/+))) were crossbred with mice that overexpress GPx-1 [GPx-1((tg+)) mice]. GPx-1 activity was 28% lower in CBS((-/+))/GPx-1((tg-)) compared with CBS((+/+))/GPx-1((tg-)) mice (P < 0.05), and CBS((-/+)) and CBS((+/+)) mice overexpressing GPx-1 had 1.5-fold higher GPx-1 activity compared with GPx-1 nontransgenic mice (P < 0.05). Mesenteric arterioles of CBS((-/+))/GPx-1((tg-)) mice showed vasoconstriction to superfusion with beta-methacholine and bradykinin (P < 0.001 vs. all other groups), whereas nonhyperhomocyst(e)inemic mice [CBS((+/+))/GPx-1((tg-)) and CBS((+/+))/GPx-1((tg+)) mice] demonstrated dose-dependent vasodilation in response to both agonists. Overexpression of GPx-1 in hyperhomocyst(e)inemic mice restored the normal endothelium-dependent vasodilator response. Bovine aortic endothelial cells (BAEC) were transiently transfected with GPx-1 and incubated with dl-homocysteine (HcyH) or l-cysteine. HcyH incubation decreased GPx-1 activity in sham-transfected BAEC (P < 0.005) but not in GPx-1-transfected cells. Nitric oxide release from BAEC was significantly decreased by HcyH but not cysteine, and GPx-1 overexpression attenuated this decrease. These findings demonstrate that overexpression of GPx-1 can compensate for the adverse effects of Hcy on endothelial function and suggest that the adverse vascular effects of Hcy are at least partly mediated by oxidative inactivation of NO.
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PMID:Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction. 1160 74


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