Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increase in antioxidant enzyme activity after acute exercise and exercise training have been reported by many investigators including our laboratory. This study was undertaken in order to determine whether an increase in activity of superoxide dismutase (MnSOD and CuZnSOD), catalase (CAT) and glutathione peroxidase (GSH-Px) during exercise training was associated with the increased levels of respective mRNAs. Male Fisher-344 rats (age 77 weeks) were given exercise training for 9 weeks on the treadmill. Enzyme activity and mRNA's were measured in the heart tissue 23 hr after stopping exercise training. The heart tissues of exercised and sedentary control rats were used to isolate mRNAs encoding MnSOD, CuZnSOD, CAT and GSH-Px by northern blotting experiments. The intensities of mRNA bands were measured by densitometric scanning of the autoradiograms. Northern blot for tubulin was used to normalize the respective intensities. Compared to sedentary controls, the level of mRNAs of enzymes MnSOD, CAT and GSH-Px were found to increase by 126 +/- 5, 133 +/- 6, and 138 +/- 5 percent of sedentary control (mean +/- SEM) respectively, due to exercise training. Corresponding values for these enzyme activity were 153 +/- 19%, 255 +/- 7%, 133 +/- 2% of sedentary control. These results suggest that post-translational modification of these enzyme activity increased in response to exercise training more than increased transcription in aged rats.
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PMID:Comparative effects of exercise training on transcription of antioxidant enzyme and the activity in old rat heart. 895 Jan 34

Although the formation of oxygen-derived free radicals (or reactive oxygen species; ROS) and the release of endogenous opioid peptides (EOP) have been independently reported to be the major arrhythmogenic factors in ischemic hearts, possible relations between these two factors have seldom been investigated. Thus, we studied whether the ROS and EOP were related in the progression of ischemia-induced arrhythmias. Isolated rat hearts perfused in the Langendorff mode were treated with dynorphin A1-13 (kappa EOP receptor agonist), and/or allopurinol (xanthine oxidase inhibitor), before the onset of ischemia induced by ligating the left coronary arteries. Ischemic period lasted for 30 min, during which cardiac rhythms were recorded. At the end of ischemia, hearts were analyzed for the glutathione and ascorbate levels. Allopurinol (100 nmoles/heart) was effective in reducing the severity of arrhythmia (arrhythmia score: Mean +/- SEM 3.00 +/- 0.80 for allopurinol, 5.75 +/- 0.41 for placebo, p < 0.01), while dynorphin (10 micrograms/heart) potentiated the arrhythmia (6.71 +/- 0.52, p < 0.05 vs. placebo). Coadministration of allopurinol and dynorphin was capable of reducing arrhythmia (5.57 +/- 0.65) when compared with the administration of dynorphin alone (6.71 +/- 0.52, p < 0.05). Tissue oxidative stress was evaluated by the concentrations of glutathione (GSH) and ascorbate. Allopurinol did not significantly elevate tissue GSH concentrations (1.46 +/- 0.05 mumoles/g wet wt) in ischemic hearts, while dynorphin alone significantly decreased the GSH concentrations (0.96 +/- 0.08, p < 0.05) when compared with the placebo (1.32 +/- 0.03). The dynorphin-induced GSH decrease cannot be reversed by coadministration with allopurinol (0.90 +/- 0.104). Allopurinol significantly elevated tissue ascorbate levels (0.16 +/- 0.01) when compared with placebo (0.10 +/- 0.01, p < 0.05). Interestingly, dynorphin alone also elevated the tissue ascorbate concentrations (0.16 +/- 0.02). Coadministration of allopurinol and dynorphin further spiked the ascorbate levels (0.28 +/- 0.05, p < 0.01). In conclusion, the results suggested that ischemia-induced arrhythmia mechanisms might involve the formation of superoxide and other ROS, which were probably generated from the release of EOP (or EOP/EOP receptor interactions). Superoxide, the formation of which can be inhibited by allopurinol that exerted antiarrhythmic effect, was probably scavenged by ascorbate in myocardial ischemia. The ROS resulting from EOP/EOP receptor interactions were probably scavenged by glutathione system. Elevated ascorbate levels in dynorphin-treated hearts might result from the compensatory synthesis induced by decreased glutathione levels.
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PMID:The roles of reactive oxygen species and endogenous opioid peptides in ischemia-induced arrhythmia of isolated rat hearts. 910 Dec 52

Epidemiologic studies have reported associations between fine particulate air pollution, especially particles less than 10 mm in diameter (PM10), and the development of exacerbations of asthma and chronic obstructive pulmonary disease. However, the mechanism is unknown. We tested our hypothesis that PM10 induces oxidant stress, causing inflammation and injury to airway epithelium. We assessed the effects of intratracheal instillation of PM10 in rat lungs. The influx of inflammatory cells was measured in bronchoalveolar lavage (BAL). Airspace epithelial permeability was assessed as total protein in bronchoalveolar lavage fluid (BALF) in vivo. The oxidant properties of PM10 were determined by their ability to cause changes in reduced glutathione (GSH) and oxidized glutathione (GSSG). We also compared the effects of PM10 with those of fine (CB) and ultrafine (ufCB) carbon black particles. Six hours after intratracheal instillation of PM10, we noted an influx of neutrophils (up to 15% of total BAL cells) in the alveolar space, increased epithelial permeability, an increase in total protein in BALF from 0.39 +/- 0.01 to 0.62 +/- 0.01 mg/ml (mean +/- SEM) and increased lactate dehydrogenase concentrations in BALF. An even greater inflammatory response was observed after intratracheal instillation of ufCB, but not after CB instillation. PM10 had oxidant activity in vivo, as shown by decreased GSH in BALF (from 0.36 +/- 0.05 to 0.25 +/- 0.01 nmol/ml) after instillation. BAL leukocytes from rats treated with PM10 produced greater amounts of nitric oxide, measured as nitrite (control 3.07 +/- 0.33, treated 4.45 +/- 0.23 mM/1 x 10(6) cells) and tumor necrosis factor alpha (control 21.0 +/- 3.1, treated 179.2 +/- 29.4 unit/1 x 10(6) cells) in culture than BAL leukocytes obtained from control animals. These studies provide evidence that PM10 has free radical activity and causes lung inflammation and epithelial injury. These data support our hypothesis concerning the mechanism for the adverse effects of particulate air pollution on patients with airway diseases.
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PMID:In vivo and in vitro proinflammatory effects of particulate air pollution (PM10). 940 Jul 38

An oxidant/antioxidant imbalance has been proposed in patients with idiopathic pulmonary fibrosis (IPF). We tested this hypothesis by measuring various parameters of the oxidant/antioxidant balance in the plasma of 12 patients with IPF (7 nonsmokers and 5 smokers); in the bronchoalveolar lavage fluid (BALF) of 24 patients with IPF (17 nonsmokers and 7 smokers) and 31 healthy subjects (23 nonsmokers and 8 smokers). The trolox equivalent antioxidant capacity (TEAC) in plasma and BALF was lower in nonsmoking patients with IPF (plasma 0.55+/-0.1 mM, p<.001; BALF 4.8+/-1.2 microM, mean +/-SEM, p<.01), compared with healthy nonsmokers (plasma 1.33+/-0.03 mM; BALF 10+/-2 microM). Similar trends in plasma and BALF TEAC were observed in smoking patients with IPF in comparison with healthy smokers. The decrease in BALF TEAC was concomitant with a decrease in BALF protein thiol levels, but the decrease TEAC levels in plasma in IPF patients was not accompanied by a decrease in protein thiol levels. Reduced glutathione (GSH) was lower in BALF in nonsmoking patients with IPF (1.0+/-0.1 microM) compared with healthy nonsmokers (2.3+/-0.2 microM, p<.001). In contrast, GSH levels were higher in smoking patients with IPF (5.2+/-1.1 microM, p<.001) than in nonsmoking patients. GSSG levels were not different in any of the groups. The levels of products of lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) in plasma and BALF were significantly increased in both smoking (plasma 2.2+/-0.5 microM, p<.01; BALF 0.18+/-0.04 microM, p<.001), and nonsmoking (plasma 2.1+/-0.3 microM, p<.01; BALF 0.22+/-0.05 microM, p<.001) IPF patients, compared with healthy nonsmokers (plasma 1.4+/-0.3 microM; BALF 0.05+/-0.004 microM). These data show evidence of oxidant/antioxidant imbalance in the lungs of patients with IPF, which is also reflected as systemic oxidant stress.
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PMID:Systemic and pulmonary oxidative stress in idiopathic pulmonary fibrosis. 1044 20

Reactive oxygen intermediates exert signalling functions and modulate gene transcription, particularly for pro-inflammatory cytokines. Since exogenous as well as endogenous thiols could be potent inhibitors of the production of cytokines, the effects of N-acetylcysteine (NAC), glutathione (GSH) and modulated GSH synthesis on the production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8 by human alveolar macrophages (AMs) was evaluated, as well as the potential role of intracellular GSH depletion on the effect of exogenous thiols. AMs were stimulated with lipopolysaccharide (LPS) and cytokine production was measured by evaluating messenger ribonucleic acid (mRNA) expression and protein secretion. Depletion of intracellular GSH by treatment with buthionine sulphoximine (BSO) reached 45.2% after 3 h and was nearly complete at 24 h. Whereas a 24-h preincubation of AMs with BSO significantly increased LPS-induced secretion of TNF-alpha and IL-8, a 3-h preincubation only enhanced LPS-stimulated production of IL-8 (p<0.05). Treatment with NAC and GSH did not significantly increase intracellular content of GSH even after a 48-h incubation. Addition of GSH and NAC significantly reduced the secretion of TNF-alpha (mean+/-SEM 21.2+/-5 and 44.7+/-4.4% inhibition, respectively) as well as LPS-induced IL-6 and IL-8 (p<0.05). Similarly, NAC inhibited the production of TNF-alpha, IL-6 and IL-8 in GSH-depleted AMs obtained by BSO pretreatment. In conclusion, N-acetylcysteine and glutathione inhibit the production of tumour necrosis factor-alpha, interleukin-8 and interleukin-6 by alveolar macrophages by a mechanism independent of glutathione metabolism. However, total depletion of glutathione within alveolar macrophages significantly increases tumour necrosis factor-alpha and interleukin-8 synthesis whereas it does not modulate interleukin-6 secretion.
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PMID:Thiol regulation of the production of TNF-alpha, IL-6 and IL-8 by human alveolar macrophages. 1048 35

Acute episodes of farmer's lung (FL) are associated with activation and migration of neutrophils into the lungs, causing oxidative stress. We conducted a study to evaluate the effect of episodes of FL on antioxidant defense of the lung by glutathione (GSH). A total of 15 patients with symptomatic FL (one female and 14 males, age 42 +/- 1 yr [mean +/- SEM]) underwent a standardized hay exposure test for 1 h and were then monitored through lung function measurements for 6 h, after which bronchoalveolar lavage (BAL) was performed. As a control, 10 asymptomatic farmers (AF) (two males and eight females, age 43 +/- 1 yr) underwent the same diagnostic procedures. At 3 to 6 h after antigen exposure, the lung function of FL patients was significantly impaired (VC: -31 +/- 4%; single-breath diffusing capacity of carbon monoxide [DL(CO)]: -17 +/- 3%; and Pa(O(2)): -14 +/- 2%, all versus baseline, whereas in AF, only minor changes occurred VC: -4 +/- 5%; DL(CO): -9 +/- 3%, and Pa(O(2)): -5 +/- 2%, all versus baseline). The number of neutrophils in bronchoalveolar lavage fluid was increased in FL patients as compared with AF (29 +/- 7 x 10(4)/ml versus 10 +/- 7 x 10(4)/ml, p < 0.05). The concentrations of total and reduced glutathione (GSH(T) and GSH, respectively) in epithelial lining fluid were decreased in FL patients and increased in AF (GSH(T): 292.5 +/- 27.5 microM versus 1, 185.0 +/- 189.9 microM, respectively, p < 0.001; GSH: 256.8 +/- 22.1 microM versus 1,054.5 +/- 172.9 microM, respectively, p < 0.001). These findings suggest that the individual ability to upregulate GSH in the alveolar space in response to an inflammatory stimulus may have implications for the development of symptomatic FL. We conclude that intrapulmonary GSH levels are distinctly different in patients with FL and AF, and that the regulation of GSH may play an important role in the pathogenesis of FL.
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PMID:Pulmonary glutathione levels in acute episodes of Farmer's lung. 1085 75

It was previously shown that 1,25-dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)) enhances the cytotoxic activity of tumor necrosis factor alpha (TNFalpha), doxorubicin and menadione. A feature shared by these anticancer agents is the involvement of reactive oxygen species (ROS) in their action. In this work we found that 1, 25(OH)(2)D(3) acted synergistically with interleukin 1 beta (IL-1beta) or interleukin 6 (IL-6) to inhibit the proliferation of MCF-7 breast cancer cells. The extent of the synergism was maximal at 1 nM, a concentration at which 1,25(OH)(2)D(3), acting singly, only marginally reduced the cell number. The thiol antioxidant, N-acetylcysteine (NAC) abolished the synergism between IL-1beta or IL-6 and 1,25(OH)(2)D(3), but had only a small protective effect when the cytokines acted alone. NAC and reduced glutathione (GSH) protected MCF-7 cells from cytotoxicity induced both by TNFalpha alone and by TNFalpha and 1,25(OH)(2)D(3). A two-day exposure to TNFalpha caused a 27.7+/-3.1% (mean +/- SEM) reduction in GSH content. This effect increased to 46.4+/-5.5% by co-treatment with 1, 25(OH)(2)D(3) which did not affect GSH levels on it own. We conclude that 1,25(OH)(2)D(3) can act synergistically with anticancer cytokines present in the tumor milieu and that ROS plays a mediatory role in this interaction.
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PMID:Synergistic anticancer activity of 1,25-dihydroxyvitamin D(3) and immune cytokines: the involvement of reactive oxygen species. 1092 9

We previously showed that cryopreservation of bull spermatozoa in egg yolk Tris extender (EYTG) significantly reduced the intracellular level of thiols. Other studies showed the beneficial effects of adding antioxidants to cryopreserved bull spermatozoa. These studies led us to investigate the effects of various thiols, an important class of antioxidants, on sperm motility of cryopreserved bull semen in a commonly used extender, EYTG. Sperm motility was analyzed by computer-assisted semen analysis (CASA). After thawing, a diluted pool of bull semen was incubated at 38.5 degrees C in airtight tubes with the following thiols for 6 hours: glutathione (GSH/GSSG), cysteine, N-acetyl-L-cysteine (NAC) and 2-mercaptoethanol in the presence or absence of oxidative stress. The oxidative stress was caused by adding H2O2 (100 microM) to diluted semen. Incubation of diluted bull semen in EYTG at 38.5 degrees C over a period of 6 h decreased sperm motility by approximately 9 fold from the start (72 +/- 3, mean +/- SEM, n=4) to the end (9 +/- 4, n=4) of the incubation. We found that all thiols to a concentration above 0.5 mM maintained high sperm motility for 6 h in the absence of an external source of oxidative stress (52 +/- 4, for 4 thiols). However, one mM of each thiol was required to efficiently protect sperm motility in the presence of 100 microM of H2O2 for 6 h. We also found that the GSH concentration in diluted semen was too low (microM) to adequately supply exogenous addition of 72 U/mL of glutathione peroxidase (GPx), an enzyme that detoxifies H2O2 and hydroperoxides using GSH as a cofactor. In fact, a better protection of sperm motility could be achieved with only 5 U/mL of GPx and 0.1 mM of GSH added to diluted semen. Our results also demonstrated that added GSSG (0.5 mM) in diluted semen was not regenerated efficiently to GSH over 6 h. The latter result indicated in the extender that the glutathione redox-cycle was deficient. Therefore, deleterious effects sperm motility after cryopreservation in EYTG can be counteracted by adding various thiols at mM concentration.
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PMID:Thiols prevent H2O2-mediated loss of sperm motility in cryopreserved bull semen. 1148 Jun 19

Calpain, a calcium activated neutral protease, is involved in mediating neurotoxicity resulting from conditions of oxidative stress and free radical formation, such as hypoxia and ischemia. Nitric oxide (NO) may also be involved in modulating the cytotoxic effects of oxidative stress. We investigated the roles of reduced glutathione (GSH), oxidized glutathione (GSSG), and NO in modulating calpain activity in PC12 cells. Cell extracts were treated with GSSG, GSH, or the NO-donor S-nitroso-N-acetylpenicillamine. Calpain activity was determined by means of a fluorescent assay. Non-linear regression analysis was used to determine the type of inhibition (competitive, uncompetitive, or non-competitive). GSH displayed uncompetitive inhibition, with K(i)=7.0+/-2.0 mM (Mean+/-SEM) while GSSG exhibited competitive inhibition with K(i)=2.5+/-0.3 mM. NO was an irreversible inhibitor of calpain activity. These results suggest that both GSH and GSSG may be important physiological modulators of calpain activity.
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PMID:Inhibition of rat PC12 cell calpain activity by glutathione, oxidized glutathione and nitric oxide. 1156 95

Oxidative stress has a key role in the pathogenesis of diabetic complications. We have previously reported that taurine (T), which is known to counteract oxidative stress in tissues (lens, kidney, retina) of diabetic rats, attenuates nerve blood flow and conduction deficits in early experimental diabetic neuropathy (EDN). The purpose of this study was to evaluate whether dietary T supplementation counteracts oxidative stress and the nerve growth factor (NGF) deficit in the diabetic peripheral nerve. The experiments were performed in control rats and streptozotocin-diabetic rats fed standard or 1% T-supplemented diets for 6 weeks. All measurements were performed in the sciatic nerve. Malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HA) were quantified with N-methyl-2-phenylindole. GSH, GSSG, dehydroascorbate (DHAA), and ascorbate (AA) were assayed spectrofluorometrically, T by reverse-phase HPLC, and NGF by ELISA. MDA plus 4-HA concentration (mean +/- SEM) was increased in diabetic rats (0.127 +/- 0.006 vs 0.053 +/- 0.003 micromol/g in controls, P < 0.01), and this increase was partially prevented by T (0.096 +/- 0.004, P < 0.01 vs untreated diabetic group). GSH levels were similarly decreased in diabetic rats treated with or without taurine vs controls. GSSG levels were similar in control and diabetic rats but were lower in diabetic rats treated with T (P < 0.05 vs controls). AA levels were decreased in diabetic rats (0.133 +/- 0.015 vs 0.219 +/- 0.023 micromol/g in controls, P < 0.05), and this deficit was prevented by T. DHAA/AA ratio was increased in diabetic rats vs controls (P < 0.05), and this increase was prevented by T. T levels were decreased in diabetic rats (2.7 +/- 0.16 vs 3.8 +/- 0.1 micromol/g in controls, P < 0.05) and were repleted by T supplementation (4.2 +/- 0.3). NGF levels were decreased in diabetic rats (2.35 +/- 0.20 vs 3.57 +/- 0.20 ng/g in controls, P < 0.01), and this decrease was attenuated by T treatment (3.16 +/- 0.28, P < 0.05 vs diabetic group). In conclusion, T counteracts oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbate system of antioxidative defense. The findings are consistent with the important role for oxidative stress in impaired neurotrophic support in EDN.
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PMID:Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy. 1168 53


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