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)

Excessive free radical formation or antioxidant enzyme deficiency can result in oxidative stress, a mechanism proposed in the toxicity of MPTP and in the etiology of Parkinson's disease (PD). However, it is unclear if altered antioxidant enzyme activity is sufficient to increase lipid peroxidation in PD. We therefore investigated if MPTP can alter the activity of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) and the level of lipid peroxidation. L-Deprenyl, prior to MPTP administration, is used to inhibit MPP+ formation and its subsequent effect on antioxidant enzymes. MPTP induced a threefold increase in SOD activity in the striatum of C57BL/6 mice. No parallel increase in GSH-PX or CAT activities was observed, while striatal lipid peroxidation decreased. At the level of the substantia nigra (SN), even though increases in CAT activity and reduction in SOD and GSH-PX activities were detected, lipid peroxidation was not altered. Interestingly, L-deprenyl induced similar changes in antioxidant enzymes and lipid peroxidation levels, as did MPTP. Taken together, these results suggest that an alteration in SOD activity, without compensatory increases in CAT or GSH-PX activities, is not sufficient to induce lipid peroxidation.
J Neurochem 1995 Dec
PMID:Effect of MPTP and L-deprenyl on antioxidant enzymes and lipid peroxidation levels in mouse brain. 759 71

This review briefly summarizes the scientific evidence for a possible role of antioxidants in the prevention of coronary heart disease (CHD). Antioxidants in our diet include vitamins E, C, and beta-carotene, whereas selenium is an integral part of the antioxidant enzyme glutathione peroxidase (GSHPx). Experimental evidence suggests that free-radical damage and antioxidant defence may play an important role in the development of coronary heart disease. Epidemiological studies have produced some intriguing results, but have not indicated unequivocally that a high intake of antioxidants leads to a decreased cardiovascular disease risk. We conclude that the antioxidant atherosclerosis hypothesis is promising, but that the results of long-term intervention studies are still to be awaited. Preventive action based on antioxidant supplementation is therefore not justifiable as yet. Nevertheless, the findings so far certainly do support the recommendations for a varied diet rich in vegetables and fruit.
Ann Med 1994 Dec
PMID:Antioxidants and coronary heart disease. 769 69

The glycoprotein, gp30, is the major soluble cuticular antigen of the adult lymphatic fiarial worm Brugia pahangi (Maizels et al., 1983, Devaney, 1988). Cookson et al., 1992 suggested that gp30 may function as an antioxidant enzyme protecting B. pahangi from the vertebrate host defence mechanism. In this communication we report that the gp30 transcript is present in each of the life cycle stages, including mosquito derived L3's, and that there is a 50 fold increase in the transcription of gp30 in young adults (28 days post infection) compared to mature adults. These findings suggest that gp30 performs a general function relevant throughout the B. pahangi life cycle and in particular to young adults.
Trop Med Parasitol 1994 Dec
PMID:Stage specific differences in steady state levels of mRNA encoding the major surface glycoprotein of Brugia pahangi. 771 3

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

Young rats are thought to be more tolerant to hyperoxia. We propose that this may not be proven and depends on how tolerance is defined. We assessed oxygen tolerance in Sprague-Dawley rats from birth to maturity by comparing survival, lung water, antioxidant enzyme activity, lung morphometrics, heart weight, and arterial blood gases in newborn and 27-, 44-, 48-, and 96-day-old rats exposed to 100% O2 or room air for 22 days. Some 96-day-old rats (rest group) received only 50% O2 between 48 and 72 h. Mortality after 5 days of O2 was 0% in newborn and 27-day-old rats and 27% in 44-day-old rats but was > 80% in 48- and 96-day-old rats. Between 5 and 22 days, the death rate was 100% in newborns, 25% in 27-day-old rats, and 0% in 44- to 96-day-old rats. Death occurred when lung water was > 84% except in newborns, which tolerated high lung water for the first 7 days. In chronically exposed 44- and 96-day-old rats, lung water returned to normal. Enzyme activity increased with O2 at all ages but did not relate to survival. In 96-day-old rats, the initial increase was suppressed on day 3. All chronically O2-exposed rats had minimal nonvascular parenchymal changes but developed right ventricular hypertrophy and increased alveolar ductal artery muscularization and lost alveolar capillaries. The most mature rats were least affected. In O2, there was pulmonary insufficiency the first 3 days, followed by recovery, and later hypercarbia and decreased arterial PO2. We conclude that young rats, 0-44 days old, are more O2 tolerant for 5 days. More mature animals, surviving 5 days, are more tolerant to chronic exposure.
J Appl Physiol (1985) 1994 Dec
PMID:Comparative age-related acute and chronic pulmonary oxygen tolerance in rats. 789 11

We have used the HL-60 and PLB-985 myeloid leukemia cell lines to examine the regulation of expression of the important intracellular antioxidant enzyme, glutathione peroxidase (GSH-Px), during phagocytic cell differentiation in vitro. Induction of differentiation along the monocytic pathway by phorbol ester results in an approximately twofold rise in enzyme activity and a parallel increase in the rate of 75Se incorporation into immunoprecipitable GSH-Px protein. Induction along the granulocytic pathway by dimethyl formamide (DMF) results in similar changes in steady-state enzyme levels and rates of GSH-Px protein synthesis. Steady-state levels of GSH-Px gene transcripts also increase more than twofold, approximately in parallel with the enzyme levels. Nuclear run-on transcription assays of GSH-Px mRNA synthesis show ratios of induced to uninduced transcript levels of 2.24 and 1.59 with phorbol myristate acetate (PMA) induction and DMF, respectively, in HL-60 cells, and ratios of 1.34 and 3.46 with PMA and DMF, respectively, in PLB-985 cells. Half lives of GSH-Px mRNA are unchanged or slightly shorter after differentiation of HL-60 cells, and slightly longer after induction of PLB-985. Overall, the present studies show that GSH-Px activity rises during in vitro-induced monocytic or granulocytic differentiation of myeloid cell lines and that the increased expression of the cellular GSH-Px gene occurs through complex mechanisms that include transcriptional up-regulation. This pattern contrasts with the nearly complete cotranslational regulation of GSH-Px expression by exogenous selenium.
Blood 1994 Dec 01
PMID:Regulation of the human cellular glutathione peroxidase gene during in vitro myeloid and monocytic differentiation. 794 46

Disulfide bonds are rarely found in cytoplasmic proteins. Mutations were selected for in Escherichia coli that allow disulfide bond formation in the cytoplasm. In the presence of these mutations, export-defective versions of alkaline phosphatase and mouse urokinase were able to fold into their enzymatically active conformations in the cytoplasm because their disulfide bonds were formed. The mutations were mapped to the gene for thioredoxin reductase and diminish or eliminate the activity of this enzyme. Thioredoxin itself was found to be unnecessary for this disulfide bond formation. Thioredoxin reductase, but not thioredoxin, is thus implicated in keeping cysteines reduced in cytoplasmic proteins.
Science 1993 Dec 10
PMID:Mutations that allow disulfide bond formation in the cytoplasm of Escherichia coli. 825 21

Selenosubtilisin, a semisynthetic enzyme produced by chemical modification of subtilisin's catalytic serine, mimics the antioxidant enzyme glutathione peroxidase, catalyzing the reduction of hydroperoxides by 3-carboxy-4-nitrobenzenethiol. In analogy with the natural peroxidase, a variety of hydroperoxides are accepted as substrates for the semisynthetic enzyme, whereas the dialkyl compound tert-butyl peroxide is not. Kinetic investigations reveal that kmax is dependent upon the nature of the hydroperoxide, indicating that peroxide-mediated oxidation of the enzymic selenolate is at least partially rate-limiting. Experiments with the radical trap 2,6-di-tert-butyl-4-methylphenol suggest that, while the nonenzymic reaction between tert-butyl hydroperoxide and thiol involves free radicals, the same reaction catalyzed by selenosubtilisin does not. The studies described here support the enzyme's proposed ping-pong mechanism and are consistent with previous mechanistic observations.
Biochemistry 1993 Dec 21
PMID:Peroxide dependence of the semisynthetic enzyme selenosubtilisin. 826 74

Controversy exists as to the effect of endurance training on myocardial antioxidant enzyme activity. These experiments sought to clarify this issue by examining antioxidant enzyme activities in the rat ventricular myocardium in response to different intensities and durations of exercise training. Female Fischer-344 rats (120 days old) were assigned to either a sedentary control group or one of nine exercise training groups. Animals were exercised on a motorized treadmill for 10 wk; combinations of three durations (30, 60, and 90 min/day), and three levels of exercise intensity (low, moderate, and high) were studied. Exercise training did not alter (P > 0.05) citrate synthase, catalase, or glutathione peroxidase activities in the right or left ventricle. In contrast, high-intensity exercise (all durations) and moderate-intensity exercise (90 min/day) resulted in a significant increase (P < 0.05; +28-30%) in right ventricular superoxide dismutase (SOD) activity. Similarly, high-intensity exercise training (all durations) resulted in a significant elevation (P < 0.05; +14-26%) of left ventricular SOD activity. Furthermore, low- and moderate-intensity exercise training of long duration (i.e., 60-90 min/day) resulted in significant increases (P < 0.05; +10-23%) in left ventricular SOD activity. These data support the hypothesis that high-intensity exercise (> or = 30 min/day) or moderate-intensity exercise of long duration (> or = 60 min/day) is effective in upregulating SOD activity in the ventricular myocardium.
Am J Physiol 1993 Dec
PMID:Rigorous exercise training increases superoxide dismutase activity in ventricular myocardium. 828 49

Using a mouse model with intraluminal blockade of the middle cerebral artery (MCA) which produced both cortical and striatal infarction, the effect that superoxide radicals have on cerebral infarction, local cerebral blood flow, and neurological deficits after 24 h of permanent focal cerebral ischemia in transgenic mice (Tg) overexpressing human CuZn-superoxide dismutase (SOD-1) was examined. There were no difference between SOD-1 Tg mice and non-Tg littermates observed in the infarct areas of brain slices, the infarct volume, the local cerebral blood flow, or the neurological deficits. These data suggest that pre-existing high levels of antioxidant enzyme failed to provide neuronal protection against permanent focal cerebral ischemia.
Neuroreport 1993 Dec 13
PMID:Brain infarction is not reduced in SOD-1 transgenic mice after a permanent focal cerebral ischemia. 829 91


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