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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now clear that peroxisomes play a crucial role in many cellular processes, including the beta-oxidation of very long chain fatty acids. Recently, mammalian peroxisomes have been shown to contain the antioxidant enzymes, superoxide dismutase and glutathione peroxidase, in addition to catalase. The presence of these enzymes in peroxisomes suggests that peroxisomes undergo oxidative stress in normal and disease states. As an indicator of the potential impact of an oxidative stress on peroxisomal functions, we evaluated the effect of endotoxin exposure on the beta-oxidation enzyme system in rat liver. Peroxisomes were isolated from liver homogenates by differential and density gradient centrifugations. Endotoxin treatment decreased the beta-oxidation of lignoceric acid to 56% of control values (p < 0.01). The specific activity of the rate limiting enzyme in the system, acyl-CoA oxidase, was decreased to 73% of control values (p < 0.05). Immunoblot analysis revealed a 25% decrease in the 21KD subunit of the acyl-CoA oxidase protein. In contrast, the protein levels of the other enzymes in the pathway, trifunctional protein and 3-ketoacyl-CoA thiolase, were increased by 10 and 15%, respectively. These findings suggest that impairment of beta-oxidation of lignoceric acid by endotoxin treatment is due primarily to a reduction in the activity and protein level of the key enzyme, acyl-CoA oxidase. Oxidative stresses such as endotoxin exposure may have deleterious effects on important peroxisomal functions, such as beta-oxidation of very long chain fatty acids.
Mol Cell Biochem 1994 Jun 29
PMID:Impairment of peroxisomal beta-oxidation system by endotoxin treatment. 783 45

The effect of dietary vitamin E supplementation upon macrophage metabolism and function was examined in aged rats fed a balanced or a polyunsaturated-rich diet. The following parameters were studied: number of cells in the intraperitoneal cavity, maximal activity of hexokinase, citrate synthase, glucose-6-phosphate dehydrogenase, glutathione peroxidase and phosphate-dependent glutaminase. The consumption of glucose and the production of lactate, hydrogen peroxide and thiobarbituric reactive substances were measured in control ONCO-BCG injected rats. The results indicated that vitamin E has no significant effect on the values of the parameters studied in the macrophages of rats fed a balanced diet both for 3 (mature) or 17 months (aged). This antioxidant did not provoke any response on the changes caused by ageing the animals. However, several of the metabolic and functional alterations in macrophage induced by the polyunsaturated-rich diets were reversed by the inclusion of vitamin E in the diet. These changes were associated with macrophage migration capacity, citrate synthase and glucose-6-phosphate dehydrogenase activities and the content of lipid peroxides. The findings suggest that vitamin E has a beneficial effect for macrophage metabolism and function, but the effects are confined to particular circumstances.
Biochem Mol Biol Int 1994 Aug
PMID:Effect of dietary vitamin E supplementation on macrophage metabolism during ageing. Study in rats fed fat-rich diets during ageing. 784 17

The growth of fibroblasts, which were isolated from human, rabbit, rat, mouse, and chick embryos, was inhibited partially under 50% oxygen and nearly completely under 95% oxygen. There was species difference in the resistivity of these cells against oxygen-induced growth inhibition. The extent of the resistivity was in the following order: chick cells > rat cells > human cells > rabbit cells approximately mouse cells. The order of their ability to recover from oxygen-induced growth inhibition was similar to the above order of species. There was also species difference in their antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase activities, and their reduced glutathione concentration. Chick cells, having the highest resistivity against oxygen-induced growth inhibition, were at the lowest activity levels of antioxidant enzymes and at the highest concentration level of reduced glutathione. The species difference in resistivity against oxygen-induced growth inhibition seems to depend on the reduced glutathione concentration, but not on the antioxidant enzyme activities.
Comp Biochem Physiol B Biochem Mol Biol 1995 Jan
PMID:Species difference in the resistibility of embryonic fibroblasts against oxygen-induced growth inhibition. 785 38

The recovery of glutathione and its metabolising enzymes (glutathione disulfide reductase, glutathione peroxidase, thiol transferase, gamma-glutamyl transpeptidase and glutathione transferase) along with sulfhydryl groups and byproduct of lipid peroxidation (malondialdehyde) in the brain, spinal cord, kidney and liver of mice, altered during methylmercury chloride (MMC) intoxication, is recorded in post-therapeutic treatment with vitamins and monothiols. For this purpose ten groups of animals were intoxicated with 1 mg/kg MMC/day for 7 days. Out of these, one group was sacrificed on 8th day and one group was kept without toxicant for another seven days before sacrificing on 15th day. Study shows significant decrease of various biomolecules of glutathione metabolism during MMC application, which are further decreased with increasing the duration on 15th day. The trend is same in all the tissues with few exceptions. However, malondialdehyde, a byproduct of lipid peroxidation, is increased with increasing the duration after intoxication. Study also shows a significant recovery (in many cases a complete control level) of most of the components with one or the other chelator or with their combined therapy. Therefore, it is concluded from overall study that vitamins B complex and E, GSH (or its precursor NAHT) either alone or in combinations, are quite suitable for methylmercury post-therapy.
Cell Mol Biol (Noisy-le-grand) 1994 Mar
PMID:Ameliorative capacities of vitamins and monothiols post therapy in the restoration of methylmercury altered glutathione metabolism. 791 95

Normal human bronchial epithelial (NHBE) cells are the putative progenitor cells of all types of lung cancer. NHBE cells immortalized by SV40 T-antigen retain many characteristics of the primary cells and are a useful model for investigating the role of oncogenes, tumor suppressor genes, and certain chemical carcinogens in the molecular pathogenesis of lung cancer. In this study, SV40 T-antigen-positive cells (BEAS-2B) were characterized for their metabolic functions and were shown to continue to express epoxide hydrolase, glutathione S-transferase pi, glutathione peroxidase, and catalase. To increase their metabolic activity towards human procarcinogens, human cytochrome P450 1A2 (CYP1A2) was stably expressed by introducing CYP1A2 cDNA into BEAS-2B cells either by infection with a high-titer recombinant retrovirus (pXT-1A2) or by transfection with a CYP1A2 expression vector (pCMV1A2), which produced the cell lines B-1A2 and B-CMV1A2, respectively. Cell lines established with either expression system expressed enzymatically active CYP1A2 protein and were 50- to 400-fold more sensitive to the cytotoxic effect of the carcinogen aflatoxin B1 (AFB1) than the corresponding control cell lines. The cytotoxic effects of AFB1 were paralleled by increased metabolism of AFB1 and enhanced formation of the AFB1-N7 guanine adduct in B-CMV1A2 cells. Cytotoxicity and adduct formation correlated with a significantly higher protein expression of CYP1A2 by the cytomegalovirus promoter-driven plasmid. Since this human epithelial cell line is the precursor cell type of lung cancer, has normal phase II enzymes, and exhibits highly reproducible expression of phase I enzymes, this in vitro model should aid in the evaluation of putative human carcinogens and anticarcinogens.
Mol Carcinog 1994 Oct
PMID:Activation of promutagens in a human bronchial epithelial cell line stably expressing human cytochrome P450 1A2. 791 94

The effects of alpha-tocopherol on the hydrazine-induced changes in the structure of mitochondria and those in the enzymatic and nonenzymatic antioxidant systems of the liver were investigated using rats as experimental animals. Animals were divided into four groups: animals of the first group were placed on a powdered diet containing 1.0% hydrazine for 7 days; those of the second and third groups received a control diet and alpha-tocopherol (ip, daily, 700 mg/kg body wt). On the fourth day and thereafter for up to 7 days, the control diet was replaced by a 1.0% hydrazine diet for the animals of the second group; those of the fourth group served as the control. After 10 days (in the case of animals of the first group, 7 days), animals were sacrificed. Results obtained were as follows: (1) Treatment of animals with alpha-tocopherol partly prevented the hydrazine-induced formation of megamitochondria in the liver. (2) Treatment of animals with hydrazine induced remarkable increases in the contents of alpha-tocopherol in mitochondria (4.8 times), microsome (1.4 times), and homogenate (2.9 times) of the liver compared with those of the control. Treatment of animals with alpha-tocopherol did not raise the concentration of alpha-tocopherol in mitochondria of the liver. The highest concentration of alpha-tocopherol in mitochondria of the liver was obtained in animals given hydrazine plus alpha-tocopherol (7.2 times higher than the control). (3) The amount of lipid-soluble fluorophores as an indicator of nonenzymatic oxidative stress was remarkably increased in mitochondria, microsome, and homogenate of the liver of hydrazine-treated animals. (4) Among enzymes protecting the cell from the oxidative stress activities of superoxide dismutase and glutathione peroxidase were almost the same among four groups of animals, while the activity of catalase was decreased distinctly in hydrazine-treated animals. Administration of alpha-tocopherol to these animals did not improve its activity. The present study has clearly demonstrated that alpha-tocopherol, a typical scavenger for free radicals, prevents the hydrazine-induced formation of megamitochondria in the liver. However, we failed to correlate free radicals to biochemical and physicochemical changes of mitochondrial membranes induced by hydrazine. Previously, we have demonstrated that a ratio of unsaturated to saturated fatty acids in phospholipid domains of mitochondrial membranes increases with hydrazine treatment. Since increases in the ratio specified above are a key event in the membrane fusion process we are now studying how the ratio is modified by hydrazine focussing on desaturase activity in the liver, and results will be reported soon.
Exp Mol Pathol 1994 Jun
PMID:Suppression of the hydrazine-induced formation of megamitochondria in the rat liver by alpha-tocopherol. 795 77

The primary defense mechanism of myocytes against peroxide-derived free radicals is the glutathione redox cycle. The purpose of the present study was to investigate whether desferrioxamine protects myocytes against peroxide-induced cell damage, and if so, whether the turnover rate of the glutathione redox cycle is involved in this protection. Neonatal rat heart cell cultures were subjected to a standardized oxidative stress by a 90 min incubation with 80 mumol/l cumene hydroperoxide. The consequences of this stress protocol were described in terms of cellular concentrations of GSH, GSSG, ATP, ATP-catabolites, and Ca2+, formation of malondialdehyde to quantify lipid peroxidation, and enzyme release to quantify the relative number of irreversibly injured cells. Following pretreatment of cell cultures with 10 mmol/l desferrioxamine mesylate for 1 h, 80 mumol/l cumene hydroperoxide caused less malondialdehyde formation (at 90 min: 0.34 v 2.35 nmol), less ATP depletion (at 60 min: 16.7 v 3.6 nmol), less Ca2+ overload (at 30 min: 40 v 1500 nM) and less enzyme release (at 90 min: 4.6 v 60.5% of the cells) compared to cell cultures subjected to cumene hydroperoxide without pretreatment. However, in desferrioxamine pretreated cell cultures cumene hydroperoxide caused cellular GSH depletion (at 60 min: 19.5 v 20.8 nmol) and GSSG efflux (at 60 min: 6.3 v 6.0 nmol) which was not different from cell cultures subjected to cumene hydroperoxide without pretreatment. Added to the finding that in a cell-free system cumene hydroperoxide is a substrate for glutathione peroxidase, we conclude that desferrioxamine, by chelating free iron ions (1), prevented the formation of cumene alkoxyl and peroxyl radicals associated with protection of the myocytes, and (2) did not diminish rapid glutathione redox cycling leading to GSH depletion and GSSG efflux.
J Mol Cell Cardiol 1994 Jul
PMID:Desferrioxamine protects myocytes against peroxide-induced myocyte damage without affecting glutathione redox cycle turnover. 796 56

The anticarcinogenic activity of alpha-tocopherol (Vitamin E) was tried in fibrosarcoma induced rats through its antioxidative potential. The rate of formation of malondialdehyde (MDA), the end product of lipid peroxidation was analysed in alpha-tocopherol (400 mg/kg body weight) treated and untreated fibrosarcoma bearing rats with respective controls. The levels of non-enzymic antioxidants like, glutathione and vitamin E, and enzymic antioxidants viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione-S-transferase (GST) were assayed as well. Significantly increased (p < 0.001) level of lipid peroxide was observed with concomitant decreases in the level of enzymic and non-enzymic antioxidants in fibrosarcoma bearing rats when compared with control animals. In alpha-tocopherol supplemented animals, the corrected level of these parameters were observed likely to near normal values. Thus, alpha-tocopherol can be accepted to pose first line of defense mechanism against excessively formed reactive species due to impaired antioxidant systems in fibrosarcoma conditions, that cause membrane damage leading to deleterious effects.
Mol Cell Biochem 1994 Feb 23
PMID:Effect of alpha-tocopherol on lipid peroxidation and antioxidant system in fibrosarcoma bearing rats. 803 77

The effects of age and hypertension on the antioxidant defence systems and the lipid peroxidation in rat isolated hepatocytes were studied. Four different age groups (1, 3, 6 and 12 months) were considered in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Age-associated changes were observed on vitamin E status, glutathione (GSH) level, MDA formation and glutathione peroxidase (GSH-Px) activity in both strains. Maximal levels or activities of these parameters were found at 3 and 6 months, except for MDA which was low at 3 months. Then, a fall was observed at 12-month-old compared to 6-month values. In addition, GSH-Px activity was significantly lower in SHR than in WKY rats, except at the age of one month. The decrease of this enzyme activity could induce an increased cellular generation of radical species and lipid peroxidation, which might be link to hypertension.
Mol Cell Biochem 1994 Mar 16
PMID:Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats. 807 5

The presence of cancer induces metabolic alterations in distant, tumor-free tissues and organs of the host. A remote humoral effect of cancer growing extrahepatically is an increase in the activity of oxidant and a decrease of antioxidant enzymes in the liver of the tumor-bearing animal. We speculated that TNF-alpha, produced by host cells, the cancer, or both, is responsible for these changes. When human recombinant TNF-alpha, 100 micrograms/kg/d i.p. for 5 days, was injected in groups of rats fed ad libitum, starved, or pair-fed, a decrease in the activity of superoxide dismutase and glutathione peroxidase and an increase in xanthine oxidase was observed, particularly with pair-fed controls. It is concluded that TNF-alpha, directly or indirectly, causes these enzyme alterations in the tumor-free liver of a tumor-bearing host.
Biochem Mol Biol Int 1994 May
PMID:TNF-alpha effect on oxygen free radical scavenging and generating enzymes in rat liver. 808 Dec 9


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