Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our studies provide evidence that thiols, such as N-acetyl-L-cysteine, inhibit both spontaneous mutations and induced mutations in bacteria, prevent the in vivo formation of carcinogen-DNA adducts, and suppress or delay the development of tumors or preneoplastic lesions in rodents. N-Acetylcysteine and other thiols exert antioxidant activity toward superoxide anion, hydrogen peroxide, and singlet oxygen, assessed in bacterial genotoxicity models. In addition, several other mechanisms were shown to contribute to their antimutagenic and anticarcinogenic activities, in the extracellular environment and in nontarget or target cells. These mechanisms include blocking of electrophilic metabolites and of direct-acting compounds, either of endogenous or exogenous source, modulation of several xenobiotic-metabolizing pathways, and protection of DNA-dependent nuclear enzymes. Chemoprevention of mutation and cancer by thiols is particularly useful under conditions of reduced glutathione (GSH) depletion due to toxic agents or to cancer-associated viral diseases, such as acquired immunodeficiency syndrome (AIDS) or viral hepatitis B.
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PMID:Antioxidant activity and other mechanisms of thiols involved in chemoprevention of mutation and cancer. 192 3

Several studies have shown that loaded breathing elicits an oxidation of reduced glutathione (GSH) to oxidized glutathione (GSSG) within the diaphragm, but the effects of loaded breathing on GSH and GSSG levels in other respiratory muscles have not been examined. The present experiment examined this issue by using decerebrate unanesthetized rats in which a large inspiratory resistive load was applied until respiratory arrest. Subsequently, muscle samples from the triangularis sterni, diaphragm (Dia), parasternal intercostal (PI), upper rib cage lateral intercostal, lower rib cage lateral intercostal, and soleus were assayed for GSH and GSSG. Glutathione levels were also measured on samples from unloaded control animals. We found that the Dia from loaded animals had a lower GSH level than did control animals (i.e., 653 +/- 99 and 928 +/- 40 nmol/gm for loaded and control groups, respectively; P < 0.05), higher GSSG level (68 +/- 14 and 32 &/- 7 nmol/gm for loaded and control groups, respectively; P < 0.05), and higher GSSG-to-GSH ratios (GSSG/GSH; 17.0 +/- 6.0 and 3.7 +/- 0.9% for loaded and control groups, respectively; (P <0.05). Of the other muscles examined, only the PI muscles had comparable alterations in glutathione levels in response to loading. Specifically, for the PI muscles of loaded and control groups, GSH was 427 +/- 75 and 618 +/- 40 nmol/g, (P < 0.05), GSSG was 71 +/- 16 and 20 +/- 5 nmol/g (P < 0.01), and GSSG/GSH was 22 +/- 8 and 3.6 +/- 1.2%, respectively (P < 0.05). No other muscle demonstrated a significant increase in GSSG or GSSG/GSH with loading, and only the lower rib cage lateral intercostal had a significant reduction in GSH. These findings indicate variation in the degree of glutathione oxidation elicited by inspiratory loading among the different respiratory muscles. The fact that quantitatively similar glutathione alterations were observed in the Dia and PI muscles suggests that these muscle groups may share a similar propensity to generate free radicals during inspiratory loading.
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PMID:Glutathione metabolic responses to loaded breathing: variation among respiratory muscles. 888 75

Effects of acute physical exercise on the acetaminophen-induced hepatotoxicity were examined in adult female rats. Rats were forced to move at a speed of 10 m/min for 2 hr in a rotating cage. Immediately following the exercise bout rats were treated with acetaminophen (APAP; 700 mg/kg, i.p.). The physical exercise enhanced the hepatotoxicity of APAP as shown by increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities measured 24 hr following the treatment. A significant decrease in hepatic glutathione (GSH) was observed in the rats forced to exercise suggesting that the enhancement of APAP hepatotoxicity was associated with the depression of this endogenous tripeptide. The role of adrenergic stimulation in the exercise-induced hepatic GSH depression was examined by pretreating the animals with a receptor specific adrenergic antagonist, such as prazosin HCl (15 mg/kg, i.p.), propranolol HCl (15 mg/kg, i.p.), and yohimbine HCl (15 mg/kg, i.p.) 15 min prior to the exercise bout, but neither of the antagonists prevented the GSH depression. Administration of alpha-tocopherol acetate (450 mg/kg/day for 3 days and 150 mg/kg on day 4, i.p.) did not affect the exercise-induced GSH depression or lipid peroxidation in liver homogenates as determined by increases in malondialdehyde formation. These results suggest that neither adrenergic stimulation nor oxidative stress plays a significant role in the enhancement of APAP hepatotoxicity and hepatic GSH depression induced by acute physical exercise.
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PMID:Potentiation of acetaminophen hepatotoxicity by acute physical exercise in rats. 917 66

Recent findings from this laboratory revealed that sleep deprivation reduces total glutathione (GSH) levels in hypothalamus, suggesting an increased vulnerability to oxidative damage. Since melatonin has been shown to prevent oxidative damage in other experimental situations, the present study tested the effects of exogenous melatonin on sleep deprivation-induced GSH decreases. Rats were deprived of sleep for 96 h on small platforms, and melatonin (10 mg/kg body weight; i.p.) or vehicle was given twice a day. Hypothalamic GSH levels were significantly reduced in sleep-deprived groups, irrespective of melatonin treatment. Indeed, unexpectedly, melatonin treatment resulted in lower hypothalamic GSH levels in all groups, including cage controls. These results confirm that sleep deprivation reduces hypothalamic GSH and further indicate that melatonin treatment not only is ineffective in reversing this effect but may actually potentiate it.
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PMID:Melatonin treatment does not prevent decreases in brain glutathione levels induced by sleep deprivation. 1070 37

The radiosensitizing effect of 5 micrograms/mL of alkaloid fraction of Alstonia scholaris (ASERS) was evaluated in various neoplastic cell lines, namely: HeLa, HePG2, HL60, MCF-7, and KB exposed to 0, 0.5, 1, 2, 3, and 4 Gy of gamma-radiation. The irradiation of various cells caused a dose-dependent elevation in the cytotoxicity, and a maximum cytotoxic effect was observed at 4 Gy (the highest dose) in all the cell lines studied. The ASERS pretreatment increased the effect of radiation as evidenced by enhanced cell killing when compared with the concurrent phosphate-buffered saline (PBS) treated irradiation group. The greatest elevation in cell killing was observed for HeLa and KB cells, followed by HL60, MCF7, and HePG2 cells. The in vitro observations were confirmed by in vivo studies, where the Ehrlich ascites carcinoma (EAC) bearing mice were treated with 120 mg/kg body weight of ASERS before exposure to 0, 1, 2, 4, 6, and 8 Gy of hemibody (below the rib cage) gamma-radiation. Irradiation of EAC mice caused a dose-dependent tumor regression, as evidenced by increased life span of the animals. The pretreatment of tumor-bearing animals with 120 mg/kg ASERS resulted in a further remission in the tumor when compared with the concurrent nondrug-treated irradiated controls; as a result there was a radiation dose-dependent increase in the life span of tumor-bearing animals receiving 120 mg/kg ASERS, except for 8 Gy, where it was less than the concurrent control. The above findings corroborate with a time-dependent decrease in the glutathione (GSH) contents, accompanied by an increase in lipid peroxidation. Our study demonstrates that ASERS treatment enhances the effect of radiation and results in disease-free survival of the mice.
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PMID:Treatment with Alstonia scholaris enhances radiosensitivity in vitro and in vivo. 1496 4

Incorporation of nitric oxide (NO) donors in non-toxic polymeric matrices can be a useful strategy for allowing topical NO delivery. We have incorporated the NO-donor S-nitrosoglutathione (GSNO) into a liquid poly(ethylene glycol) (PEG)/H2O matrix through the S-nitrosation of GSH by a NO/O2 gas mixture. Kinetic measurements of GSNO decomposition associated with NO release were performed at 25, 35, and 45 degrees C in the dark and under irradiation with UV/Vis light, lambda>480 nm and lambda=333 nm. NO release from the liquid matrix to the gas phase was confirmed by mass spectrometry. The PEG/H2O matrix stabilizes GSNO leading to expressive reductions in the initial rates of thermal and photochemical NO release, compared to aqueous GSNO solution. This matrix effect is assigned to diffusional constrains imposed on the escape of the NO and GS radicals formed in the solvent cage. This effect allows the storage of PEG-GSNO formulations for extended periods (more than 65 days at freezer) with negligible decomposition. PEG-GSNO formulation seems therefore to be applicable in topical NO delivery and GSNO displays potential as a percutaneous absorption enhancer. Moreover, the rate of NO release can be locally increased by irradiation with visible light.
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PMID:S-nitrosoglutathione incorporated in poly(ethylene glycol) matrix: potential use for topical nitric oxide delivery. 1556 73

Pateira de Fermentelos (PF) is a natural freshwater wetland in the central region of Portugal. In the last decade, the introduction of agricultural chemicals, heavy metals, domestic wastes, as well as eutrophication and incorrect utility of resources resulted in an increased water pollution. The present research work was carried out to check the various oxidative stress biomarker responses in European eel (Anguilla anguilla L.) gill, kidney and liver due to this complex water pollution. Eels were caged and plunged at five different PF sites (A-E) for 48h. A reference site (R) was also selected at the river spring where no industrial contamination should be detected. Lipid peroxidation (LPO), catalase (CAT), glutathione peroxidase (GPX), glutathione S-transferase (GST) and reduced glutathione (GSH) were the oxidative stress biomarkers studied. In gill, site A exposure induced a significant GST activity increase and site B exposure induced CAT activity increase when compared to R. Site C exposure showed a significant CAT and GPX activity increase. Data concerning site D exposure were not determined due to cage disappearance. Site E exposure displayed a significant CAT and GST activity increase. In kidney, site A exposure induced a significant CAT and GPX decrease as well as a GST increase. Site B exposure showed a significant decrease in GPX activity and GSH content. However, site C exposure demonstrated a significant increase in CAT and a decrease in GPX. Site E exposure showed a significant decrease in GPX and increase in GST. In liver, site A exposure showed a significant GST activity decrease as well as GSH content increase. Site B exposure showed a significant CAT, GST and LPO decrease. Site C exposure showed only GST activity decrease, while site E exposure induced a significant increase in GPX. These investigation findings provide a rational use of oxidative stress biomarkers in freshwater ecosystem pollution biomonitoring using caged fish, and the first attempt reported in Portugal as a study of this particular watercourse under the previous conditions. The presence of pollutants in the PF water was denunciated even without a clear relation to the main pollution source distance. The organ specificity was evident for each parameter but without a clear pattern.
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PMID:Anguilla anguilla L. oxidative stress biomarkers: an in situ study of freshwater wetland ecosystem (Pateira de Fermentelos, Portugal). 1672 79

The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC) housed in home cage and left in the laboratory; restrained rats (with three subgroups) subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC) having their restrainers kept in the laboratory; restrained pyramid rats (RP) being kept in the pyramid; and restrained square box rats (RS) in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA) and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH) levels, erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.
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PMID:Housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats. 1734 39

Physiological and biochemical responses of four fishes with different trophic levels to toxic cyanobacterial blooms were studied in a large net cage in Meiliang Bay, a hypereutrophic region of Lake Taihu. We sampled four fishes: the phytoplanktivorous Hypophthalmichthys molitrix and Aristichthys nobilis, the omnivorous Carassius auratus, and the carnivorous Culter ilishaeformis. Alterations of the antioxidant (GSH) and the major antioxidant enzymes (CAT, SOD, GPx, GST) in livers were monitored monthly, and the ultrastructures of livers were compared between the bloom and post-bloom periods. During the cyanobacterial blooms, the phytoplanktivorous fishes displayed only slight ultrastructural changes in liver, while the carnivorous fish presented the most serious injury as swollen endomembrane system and morphologically altered nuclei in hepatocytes. Biochemically, the phytoplanktivorous fishes possessed higher basal GSH concentrations and better correlations between the major antioxidant enzymes in liver, which might be responsible for their powerful resistance to MCs. This article provided physiological and toxicological evidences for the possible succession of fish communities following occurrence of toxic cyanobacterial blooms and also for the applicability of using phytoplanktivorous fish to counteract toxic cyanobacterial blooms in natural waters.
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PMID:In situ studies on physiological and biochemical responses of four fishes with different trophic levels to toxic cyanobacterial blooms in a large Chinese lake. 1757 63

A novel Gd(III) complex with a modified DO3A-like chelating cage has been synthesized and characterized as a candidate contrast agent responsive to the concentration of free thiols in tissues (essentially represented by reduced glutathione, GSH). The novel compound (called Gd-DO3AS-Act) bears a flexible linker ending with a 2-pyridyl-dithio group, that can promptly react with free thiols (XSH) to form mixed disulfides of the form Gd-DO3AS-SX. Compound Gd-DO3AS-Act is characterized by a millimolar relaxivity as high as 8.1 mM(-1) s(-1) (at 20 MHz, 25 degrees C and pH 7.4). Upon reaction with GSH, the Gd-DO3AS-SG covalent adduct is formed and the millimolar relaxivity drops to 4.1 mM(-1) s(-1). Such a decrease in relaxivity is explained on the basis of the formation of an intramolecular coordinative bond between one of the glutathionyl carboxyl groups and the Gd(III) centre, lowering the hydration state of the paramagnetic centre. (1)H-NMR dispersion profiles together with (17)O-NMR transverse relaxation time versus temperature profiles confirm that the hydration of the Gd(III) centre is strongly reduced ongoing from Gd-DO3AS-Act to the Gd-DO3AS-SG adduct. The relaxivity difference brought about by the reaction of Gd-DO3AS-Act with GSH can be enhanced up to 60% in the presence of poly-beta-cyclodextrin.
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PMID:Synthesis and characterization of a Gd(III) based contrast agent responsive to thiol containing compounds. 1799 83


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