Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased oxidative stress resulting from free radical damage to cellular function is associated with a number of neurodegenerative diseases, in particular with Alzheimer's disease (AD). The deposition of amyloid beta-peptide (Abeta), the major pathological hallmark for AD, has been suggested as the central disease-causing and disease-promoting event for the disease, and the pathological role of Abeta was partially mediated by oxidative stress. Here we compared the effects of huperzine A (HupA) and tacrine, two acetylcholinesterase (AChE) inhibitors available for AD, on Abeta-induced cell lesion, level of lipid peroxidation, and antioxidant enzyme activities in rat PC12 and primary cultured cortical neurons. Following exposure of both cells to different concentrations of an active fragment of Abeta, a marked reduction in cell survival and activities of glutathione peroxidase (GSH-Px) and catalase (CAT), as well as increased production of malondialdehyde (MDA) and superoxide dismutase (SOD), were observed. Pretreatment of the cells with HupA or tacrine (0.1-10 microM) prior to Abeta exposure significantly elevated the cell survival and GSH-Px and CAT activities and decreased the level of MDA. Both drugs have similar protection against Abeta insult. Our results indicate that HupA and tacrine exert neuroprotective effects against Abeta toxicity, which might be of importance and might contribute to their clinical efficacy for the treatment of AD.
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PMID:Huperzine A and tacrine attenuate beta-amyloid peptide-induced oxidative injury. 1095 26

We have previously demonstrated that the loss of glutathione (GSH) and GSH-peroxidase (GSH-PX) in banked red blood cells (RBCs) is accompanied by oxidative modifications of lipids, proteins and loss of membrane integrity. The objective of this study was to determine whether artificial increases in antioxidant (GSH) or antioxidant enzyme (catalase) content could protect membrane damage in the banked RBCs following an oxidant challenge. RBCs stored at 1-6 degrees C for 0, 42 and 84 days in a conventional additive solution (Adsol) were subjected to oxidative stress using ferric/ascorbic acid (Fe/ASC) before and after enriching them with GSH or catalase using a hypotonic lysis-isoosmotic resealing procedure. This lysis-resealing procedure in the presence of GSH/catalase raised intracellular GSH and catalase concentrations 4-6 fold, yet produced only a small reduction in mean cell volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentrations (MCHC). Indicators of oxidative stress and membrane integrity were measured, including acetylcholinesterase (AChE) activity, GSH concentration, phosphatidylserine (PS) externalization (prothrombin-converting activity) and transmembrane lipid movements (14C-lyso phosphatidylcholine flip-flop and PS transport). GSH-enrichment protected AChE activity in fresh (0 day) and stored (42 and 84 days) RBCs from Fe/ASC oxidation by 10, 23 and 26%, respectively, compared with not-enriched controls. Following oxidative stress, the rate of transbilayer lipid flip-flop did not increase in fresh cells, but increased 9.3% in 42-day stored cells. Phosphatidylserine exposure, as measured by prothrombinase activity, increased 2.4-fold in fresh and 5.2-fold in 42-day stored cells exposed to Fe/ASC. Previous studies have shown that 42-day storage causes a moderate decrease in PS transport (approximately 50%), whereas transport rates declined by up to 75% in stored RBCs when challenged with Fe/ASC. GSH-enrichment prevented the increase in passive lipid flip-flop and the increase in prothrombinase activity, but offered no protection against oxidative damage of PS transport. In contrast to these effects, catalase-enrichment failed to protect GSH levels and AChE activity upon oxidative stress. Membrane protein thiol oxidation was assessed by labeling reactive protein thiols with 5-acetalamidofluorescein followed by immunoblotting with antifluorescein antibodies. Significant oxidation of membrane proteins was confirmed by a greater loss of thiols in stored RBCs than in fresh RBCs. These results demonstrate that it may be possible to prevent storage-mediated loss of AChE, increased lipid flip-flop, and increased PS exposure, by maintaining or increasing GSH levels of banked RBCs.
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PMID:Glutathione loading prevents free radical injury in red blood cells after storage. 1120 85

Anilofos and isoproturon are important herbicides of organophosphorus and substituted phenylurea groups, respectively. Isoproturon is an inducer of hepatic drug-metabolizing enzymes. Animals and humans have the potential to be exposed to the mixture of these intentionally introduced environmental xenobiotics, but toxicological interactions between these herbicides are not known. Effects of isoproturon pretreatment (675 mg/kg/day for 3 consecutive days) on the toxic actions of anilofos administered orally as a single dose (850 mg/kg) were evaluated by determining some biochemical attributes in blood (erythrocyte/plasma), brain and liver of rats. Anilofos or isoproturon alone or in combination failed to produce any noticeable signs of cholinergic hyperactivity and behavioural alterations. Isoproturon did not potentiate the anticholinesterase action of anilofos in blood and liver. Inhibition of brain acetylcholinesterase was significantly protected. No significant alteration in anilofos-mediated production of lipid peroxidation was observed in erythrocyte and brain of isoproturon-pretreated rats, but it was significantly increased in liver. Anilofos did not affect GSH and GST. The isoproturon-mediated increase in GSH levels of brain (threefold) and liver (3.6-fold) was also not affected following combined administration. GST activity was increased in liver of rats given isoproturon alone (fourfold) or in combination with anilofos (2.8-fold). Activities of total ATPase, Mg2+-ATPase and Na+-K+-ATPase were not affected in rats given either anilofos alone or herbicides in sequence. With these treatments, there were no alterations in the protein content of plasma, brain and liver. Overall findings of the study indicate that isoproturon pretreatment does not alter the toxicity of anilofos, the GSH-GST metabolic pathway may not have a significant implication in the detoxification of anilofos and the production of a reactive oxygen species may be a factor in mediating anilofos toxicity.
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PMID:Effect of isoproturon pretreatment on the biochemical toxicodynamics of anilofos in male rats. 1152 67

We studied the effects, at 10 and 30 min, of a single dose (10 mg kg(-1)) of lead chloride, administered by the intraperitoneal route, on the activities of acetylcholinesterase (AChE) and glutathione transferase (GSH-T) and on the concentrations of total and non-protein thiols in substantia nigra compacta (SNCO) and substantia nigra reticulata (SNRE), caudate putamen (CAU) and cerebral cortex (CC) from adult male rats in comparison with the effects of this metal at 24 and 72 h. The main immediate effects of lead consisted of decreased GSH-T activity and total and non-protein thiol concentrations in CAU and CC 10 min after administration. These effects were reversed after 30 min but with increased GSH-T activity in SNCO and AChE activity in SNRE along with diminished concentration of homogenate proteins in SNRE, CAU and CC. The GSH-T activity again was increased in SNCO but the AChE activity was decreased in CC 24 h after Pb administration; total and non-protein thiol concentrations were diminished but homogenate protein concentration was augmented in all areas. Finally, 72 h after Pb administration, AChE and GSH-T activities were decreased in CAU and CC, accompanied by an increased concentration of precipitate and supernatant proteins; supernatant protein concentration also was augmented in SNCO and SNRE; here, again, the concentrations of total and non-protein thiols were diminished and the homogenate protein concentration was augmented in all areas.
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PMID:Immediate and delayed effects of lead on AChE, GSH-T and thiols in the substantia nigra, neostriatum and cortex of the rat brain. 1174 81

Biomonitoring organophosphate (OP) exposure in marine environments is generally achieved by the measurement of acetylcholinesterase activity in bivalves like mussels. However, there is evidence that indicates that oxidative stress may be implied in OP toxicity. The aim of this study was to evaluate the relationship between survival from the OP insecticide fenitrothion and glutathione levels in marine bivalves. Mussels (Mytilus galloprovincialis Lam.) and scallops (Flexopecten flexuosus Poli) were exposed, in a time to death test, to their LC85 of fenitrothion for 96 h. OP-poisoned mussels showed reduced (GSH) and oxidised (GSSG) glutathione depletion in the digestive gland, muscle and gills. Pectinid spats exposed to this insecticide presented GSH depletion in the digestive gland and mantle, and a reduction of the GSH/GSSG ratio in gills and mantle. Although survival curves were significantly different and mussels withstood twice as much fenitrothion as pectinid spats, muscular GSH/GSSG ratio was highly related to mortality in both species. We suggest that an impairment in the glutathione redox status could result in an induction of the cell death, either by apoptosis or necrosis, leading ultimately to the death of the organism. We conclude that whereas glutathione depletion can be used as a biomarker of exposure, the muscular GSH/GSSG ratio might be used as a biochemical marker of effect and individual susceptibility to mortality of marine bivalves exposed to fenitrothion or other pollutants that induce oxidative stress.
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PMID:Impaired glutathione redox status is associated with decreased survival in two organophosphate-poisoned marine bivalves. 1199 24

The biochemical effects of the 2-nitroimidazole hypoxic cell radiosensitizers KIN-804, KIN-806, and their analogues KIN-844 and TX-1877 on brain acetylcholinesterase (AChE) and hepatic free radical scavenging systems, such as reduced glutathione (GSH) and glucose-6-phosphate dehydrogenase (G-6-PDH) levels, and hepatic antioxidants, such as superoxide dismutase (SOD) and catalase, were evaluated in Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. The assay of brain AChE revealed nonsignificant changes with all drugs examined. To evaluate the hepatic metabolic capacity, groups of mice were divided into control, EAC-inoculated, 10-Gy local gamma-irradiated, and KIN-804, KIN-844, KIN-806, or TX-1877 (50 mg/kg body weight, i.p.) groups, and gamma-irradiation was combined with each drug. EAC inoculation markedly suppressed GSH, G-6-PDH, SOD, and catalase levels. On the other hand, treatment with gamma-irradiation significantly enhanced them. The treatment of EAC-bearing mice with each drug alone in the absence of gamma-irradiation revealed that KIN-806 and its derivative TX-1877 showed antitumor activity through their significant recovery of GSH and SOD levels, respectively, in the EAC-bearing mice group. Similarly, the combined treatment of EAC-bearing mice with gamma-irradiation with each of the drugs tested showed that KIN-806 and TX-1877 significantly increased GSH and SOD, and to a lesser extent G-6-PDH and catalase levels. On the other hand, KIN-804 and KIN-844 had only a nonsignificant effect on all parameters examined. In conclusion, these data reveal that the administration of KIN-806 and TX-1877 with or without subsequent gamma-irradiation, resulted in significant recovery of GSH and SOD activities that were inhibited by EAC inoculation.
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PMID:Comparison of hypoxic cell radiosensitizers, KIN-804, KIN-844, KIN-806 and TX-1877, on brain and liver metabolizing capacities in mice bearing Ehrlich ascites carcinoma. 1203 98

Erythrocyte osmotic fragility (O.F.), acetylcholinesterase (AChE) activity, and the level of malonyl dialdehyde (MDA) of control, mefenamic acid treated, and mefenamic acid with vitamin E treated rats were investigated. Administration of mefenamic acid to albino rats brought about a significant increase in the osmotic fragility of red cells and a significant (p < 0.01) decrease in the activity of AChE. We have also observed increased red cell level of MDA and decreased cholesterol (Chl), hemoglobin (Hb), and reduced glutathione (GSH) content. Supplementation of vitamin E to the mefenamic acid treated rats restored the O.F., AChE activity, level of MDA, and Chl, Hb, and GSH content almost to normal. These observations suggest that mefenamic acid causes functional impairment of red cell membrane, while vitamin E shows its protective role in maintaining normal red cell functions.
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PMID:Protective role of vitamin E on mefenamic acid-induced alterations in erythrocytes. 1222 96

Many organophosphorus (OP) compounds are of the thiono form and in insects or animals are converted by microsomal mixed function oxidases (MFO) into the oxon forms which inhibit acetylcholinesterase (AChE) and give toxic activity. However, certain S-alkyl phosphorothiolates (RS-P(O) <) such as methamidophos, profenophos and prothiophos oxon are strongly insecticidal, but very poor inhibitors of AChE in vitro. Their oxons are converted further to the S-oxides, which either inhibit AChE or decompose, depending on the alkyl substituents on the sulfur atom. It is also inferred in the case of prothiophos oxon that its S-oxide not only inhibits AChE but also conjugates with glutathione (GSH) by the action of glutathione S-transferase (GST), and the conjugate inhibits AChE. Certain phosphoramidates (R2N-P(O) <) such as isofenphos oxon, schradan and propetamphos oxon are weak AChE inhibitors, but strongly insecticidal. It is well known that isofenphos oxon is converted into the stable N-desalkyl form (H2N-P(O) <) by oxidative dealkylation to inhibit AChE. The authors have studied activation of phosphoramidates using 2,4-dichlorophenyl methyl N-alkylphosphoramidates as model compounds using various approaches including computational chemistry, and these studies indicated that the O-aminophosphate structure (R2N-O-P(O) <) is an activated form.
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PMID:Activated transformations of organophosphorus insecticides in the case of non-AChE inhibitory oxons. 1244 29

The use of biomarkers to evaluate the biological effects of chemical pollutants in marine organisms represents a recent tool in the monitoring field responding to the need to detect and assess the effects of chemical contaminants on the biota. The aim of the present work was the field application of the integrated use of acetylcholinesterase (AChE) and antioxidant enzymes (catalase--CAT, glutathione peroxidase--GSH-Px), for detecting the possible exposure/effect induced by chemical pollutants in native marine organisms from a coastal marine area, represented by Salento Peninsula (Italy), that shows a coastline of high environmental value, but under constant urban pressure, including agriculture activities, widely diffused in the whole hinterland. Eight sampling stations were chosen: four not urbanized areas considered "uncontaminated" controls and four clearly exposed to anthropogenic impact. The bioindicator species studied were a sessile invertebrate, Mytilus galloprovincialis, and a benthic teleost fish, Mullus barbatus.AChE activity in M. galloprovincialis revealed significant differences among places; the minimum values observed (3.9+/-1.8 nmolmin(-1)mg(-1)) was about 50% reduced with respect to the maximum found (11.4+/-0.9 nmolmin(-1)mg(-1)). The reduction in AChE activity observed in two control stations could be explained by the leaching of pesticides into the sea from the agricultural lands. Moreover, the inhibition of AChE activity by heavy metals besides pesticides, can also explain the reduction of the enzymatic activity observed in an industrialized and harbour area. In M. galloprovincialis AChE activity showed a significant inverse correlation with catalase activity but not with glutathione peroxidase that did not significantly change in animals sampled from the eight stations. Also in M. barbatus AChE activity showed significant differences among places; it was inversely correlated with liver GSH-Px activity, but not with catalase activity, that did not show any significantly variation in animals sampled in the different stations. In conclusion, the integrated use of AChE and antioxidant enzymes (catalase or glutathione peroxidase) in M. galloprovincialis and M. barbatus, two species living in different compartment of marine coastal ecosystem, can find a useful application within the framework of marine coastal environment monitoring programs for detecting the possible exposure/effect induced by chemical pollutants, including pesticides, on living marine organisms.
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PMID:Integrated use of biomarkers (acetylcholinesterase and antioxidant enzymes activities) in Mytilus galloprovincialis and Mullus barbatus in an Italian coastal marine area. 1260 66

Within the pulmonary epithelial lining layer (ELF), antioxidants such as ascorbic acid (AH(2)) and glutathione (GSH) react with inhaled nitrogen dioxide ((*)NO(2)) to produce reactive oxygen species (ROS) that induce cellular oxidation. Because the ELF contains unsaturated fatty acids (UFA), which potentially react with (*)NO(2) and/or the antioxidant-derived ROS, we studied the influence of aqueous phase model UFA [egg phosphatidylcholine (EggPC) liposomes] on exposure-induced oxidation and nitration of membranes. Our lung surface model used gas phase (*)NO(2) exposures of immobilized red cell membranes (RCM) overlaid with defined aqueous phases. Acetyl cholinesterase (AChE) activity, TBARS, and 3-nitrotyrosine (3-NT) were used to assess protein and lipid oxidation and RCM nitration, respectively. During (*)NO(2) exposure, AH(2) and GSH induced AChE loss and TBARS, which were unchanged with buffer only. Exposures of EggPC generated extensive TBARS but not AChE loss; addition of AH(2)/GSH to EggPC resulted in smaller AChE declines and fewer TBARS. 3-NT formation occurred with or without EggPC, low concentration antioxidants, SOD, catalase, or DTPA, but was inhibitable by desferrioxamine or high antioxidant concentrations. The data suggest that reaction/diffusion limitations govern (*)NO(2) distribution, that (*)NO(2) per se directly nitrates tyrosine residues within hydrophobic regions, and that the induction of secondary oxidative processes is dependent on nonlinear relationships among (*)NO(2) flux rates, antioxidant concentrations, and diffusivity of secondary reactive species.
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PMID:Influence of epithelial lining fluid lipids on NO(2)-induced membrane oxidation and nitration. 1263 49


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