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AChE Activity (ache + activity)
Selected AbstractsComparing the relative toxicity of malathion and malaoxon in blue catfish Ictalurus furcatusENVIRONMENTAL TOXICOLOGY, Issue 4 2008Winfred G. Aker Abstract Malathion inhibits the critical body enzyme, acetylcholinesterase (AChE). This capability requires that malathion should first be converted to malaoxon to become an active anticholinesterase agent. Conversion can be caused by oxidation in mammals, insects, plants, and in sunlight. In this study, the effects of malathion and malaoxon on catfish Ictalurus furcatus were evaluated. After 96-h exposures, the LC50 (concentration that causes 50% mortality) and IC50 (concentration that causes 50% enzyme inhibition) for malaoxon were lower than corresponding values for malathion. The overall mean 96-h LC50 is 17.0 ppm for malathion and 3.1 ppm for malaoxon. IC50 values for malathion are 8.5 ppm for brain, 10.3 ppm for liver, and 16.6 ppm for muscle. Corresponding values for malaoxon are 2.3, 3.7, and 6.8 ppm, respectively. All the AChE activities in malathion- and malaoxon-exposed catfish brain showed significant inhibition. The oxidation product malaoxon demonstrated higher inhibition on AChE activity than did malathion. Moreover, malaoxon showed significant inhibition on butyrylcholinesterase (BChE) in the liver if the concentrations were increased to more than 1 ppm. Malathion showed no difference between treatment group and control group. Compared with malathion, malaoxon showed higher inhibition on monoamine activity than that of malathion. The results indicated that the oxidative product malaoxon is more toxic than the parent compound malathion. AChE, BChE, and monoamine activities are confirmed as bioindicators of malathion exposure in blue catfish, I. furcatus. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source] Multimarker approach in transplanted mussels for evaluating water quality in Charentes, France, coast areas exposed to different anthropogenic conditionsENVIRONMENTAL TOXICOLOGY, Issue 5 2003M. Roméo Abstract An active biomonitoring experiment was performed using mussels collected at a clean site, Fier d'Ars, and transplanted to two locations, outside the harbor of La Rochelle and in the Baie de L'Aiguillon along the coast of Charentes (French Atlantic coast) beginning in April for several months. Mussels were collected in June and October. The cadmium, copper, and zinc concentrations of all resident and transplanted mussel samples and the polycyclic aromatic hydrocarbon and polychlorinated biphenyl concentrations in some mussel samples and in the sediment samples were determined. Mussel response was evaluated for several biochemical biomarkers: concentrations of metallothionein, activities of glutathione S-transferase and acetylcholinesterase (AChE) and levels of thiobarbituric reactive substance (TBARS). The physiological status of the animals was assessed using the condition index. A principal component analysis performed with the chemical and biochemical results of the evaluations of the resident and transplanted mussels collected in June allowed them to be separated into three groups: resident mussels from la Rochelle with high metal and TBARS levels, resident mussels from Baie de L'Aiguillon with a very high condition index, and resident mussels from Fier d'Ars and transplanted mussels at La Rochelle and Baie de L'Aiguillon with low TBARS and AChE activities. Strong seasonal variation from June to October of all parameters was noted. Mussels transplanted to La Rochelle appeared to be the most "polluted" in their pollutant concentrations and biochemical responses; moreover, the La Rochelle site had the highest concentration of organics in sediments of all the sites. The choice of Fier d'Ars as a reference site may be questionable because some of the biomarker responses of the mussels were higher than expected there, although these pollutants in mussels and sediment were present at the lowest concentrations measured. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 295,305, 2003. [source] Effects of Anabaena spiroides (cyanobacteria) aqueous extracts on the acetylcholinesterase activity of aquatic speciesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2001José María Monserrat Abstract The effects of aqueous extracts from a cyanobacteria species, Anabaena spiroides, on fish (Odontesthes argentinensis), crab (Callinectes sapidus), and purified eel acetylcholinesterase (AChE) activity were studied. In vitro concentrations of A. spiroides aqueous extract that inhibited 50% of enzyme activity (IC50) were 23.0, 17.2, and 45.0 mg/L of lyophilized cyanobacteria for eel, fish, and crab AChE, respectively. Eel AChE inhibition follows pseudo-first-order kinetics, the same expected for organophosphorus pesticides. Inhibition of purified eel AChE using mixtures of bioxidized malathion and aqueous extract of A. spiroides showed a competitive feature (p < 0.05), suggesting that the toxin(s) could be structurally similar to an organophosphorus pesticide and that toxins present in the aqueous extract inhibit the active site of the enzyme. The inhibition recovery assays using 2-PAM (0.3 mM) showed that (1) bioxidized malathion inhibited 27.0 ± 1.1% of crab and 36.5 ± 0.1% of eel AChE activities; (2) with bioxidized malathion + 2-PAM the registered inhibition was 13.2 ± 2.1% and 3.7 ± 0.5% in crab and eel AChE, respectively; (3) the aqueous extract from A. spiroides inhibited 17.4 ± 2.2% and 59.9 ± 0.5% of crab and eel AChE activity, respectively; and (4) aqueous extract + 2-PAM inhibited 22.3 ± 2.6 and 61.5 ± 0.2% of crab and eel AChEs. The absence of enzyme activity recovery after 2-PAM exposure could imply that the enzyme aging process was extremely quick. [source] ORIGINAL ARTICLE: Brain and hypophyseal acetylcholinesterase activity of pubertal boars fed dietary fumonisin B1JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 5 2010F. A. Gbore Summary The effects of dietary fumonisin B1 (FB1) on regional brain and hypophyseal activities of AChE (EC 3117), the enzyme which catalyses the hydrolysis of acetylcholine, were studied using 24 male Large White weanling pigs divided into four groups. Each group received one of the four diets containing 0.2, 5.0, 10.0 and 15.0 mg FB1/kg in a 6-month feeding trial. All animals were slaughtered at the end of the feeding trial; the brains and the hypophyses obtained were carefully dissected out. Significant (p < 0.05) influence of dietary FB1 on regional brain and hypophyseal AChE activities were observed. The AChE activities in the pons, amygdala, hypothalamus and the medulla oblongata declined significantly (p < 0.05) with increased dietary FB1 concentrations. The findings of this study suggest that diets containing 5.0 mg FB1/kg and above significantly (p < 0.05) altered regional brain and hypophyseal AChE activities in the animals. Dietary exposure to FB1 at a concentration of approximately 5.0 mg/kg or more for a 6-month period is a potential health risk that may induce adverse physiological response resulting from altered brain neurochemistry in growing pigs. [source] Immunotoxicity of acute acephate exposure in control or IL-1-challenged rats: correlation between the immune cell composition and corticosteroid concentration in bloodJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2002Ashok K. Singh Abstract Corticosterone concentration and the immune cell composition were measured in rats exposed by intraperitoneal (i.p.) injection to different doses (10,500 mg kg,1) of acephate (Ace) and 250 µg kg,1 of interleukin 1 (IL-1), either alone or in combination. Two different combination protocols were used: IL-1 and Ace were administered simultaneously; and IL-1 was injected 60 min after Ace administration (sequential exposure). Ace, in a dose- and time-dependent manner, inhibited blood and brain acetylcholinesterase (AChE) activities, increased blood corticosterone concentrations, suppressed blood CD4, CD8, B cell and monocyte contents and increased blood neutrophil counts. The Ace-induced changes lasted for up to 24 h after Ace exposure. Interleukin 1 increased blood corticosterone concentrations without affecting blood or brain AChE activities. The IL-1-induced corticosterone concentration returned to the basal level within 3,10 h after IL-1 exposure. The CD4, CD8, B cell and monocyte counts increased significantly at 10 min after IL-1 exposure. The cell counts decreased gradually thereafter and returned to the basal level within 30 min after IL-1 exposure. Simultaneous exposure of rats to Ace and IL-1 partially suppressed the IL-1-induced increase in the immune cell counts and decreased the immune cell numbers below the basal values. Sequential injection of Ace and IL-1 blocked the IL-1-induced increase in the immune cell numbers. Thus, Ace exposure would impair the normal distribution of immune cells and deregulate the IL-1 response in rats. This study therefore suggests that Ace would suppress the immune cell numbers in blood, thus decreasing an organism's immunity. Ace exposure occurring concurrent with injury would augment the acute-phase response, which would augment the toxic effects of IL-1 and other cytokines, and Ace exposure occurring prior to the injury would suppress or abolish the initial stimulatory effects of IL-1, which would decrease an organism's ability to combat infection or injury. Copyright © 2002 John Wiley & Sons, Ltd. [source] Effects of hunger level and nutrient balance on survival and acetylcholinesterase activity of dimethoate exposed wolf spidersENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 3 2002Lars-Flemming Pedersen Abstract The influence of two nutritional factors (food quantity and quality) on the responses of a wolf spider, Pardosa prativaga (L.K.), to a high dose of the insecticide dimethoate, was investigated in a fully factorial experimental design. Spider groups with different (good and bad) nutrient balance were created by feeding them fruit flies of either high or low nutrient content for 28 days. Both groups were then split into satiated and 14 days starved subgroups. Each of these was further divided into insecticide treated and control halves. Survivorship and acetylcholinesterase (AChE) activity measured on the survivors were used as response variables. Survivorship after topical dimethoate exposure (LD50; 48 h) was influenced by spider body weight, nutrient balance, and starvation. Furthermore, AChE activity was significantly inhibited by dimethoate exposure. A significant interaction between nutrient balance, starvation, and dimethoate exposure revealed synergistic effects of starvation and nutrient imbalance on AChE inhibition by dimethoate in surviving spiders. These results show that the tolerance of non-target arthropods to dimethoate may vary depending on the nutritional history of the animal. [source] Effects of exposure to oxamyl, carbofuran, dichlorvos, and lindane on acetylcholinesterase activity in the gills of the Pacific oyster Crassostrea gigasENVIRONMENTAL TOXICOLOGY, Issue 4 2010Gerardo A. Anguiano Abstract Acetylcholinesterase (AChE) activity has been used to test the exposure of mollusk bivalves to pesticides and other pollutants. The Pacific oyster Crassostrea gigas is a species with a worldwide distribution, and it has a high commercial value. The use of this species as a bioindicator in the marine environment, and the use of measurements of AChE activity in tissues of C. gigas require prior evaluation of organisms exposed to several toxic compounds in the laboratory. In our study, the effects of pesticides on AChE activity in the gills and mantle tissues of C. gigas were analyzed by exposing animals to organophosphate (dichlorvos), carbamate (carbofuran and oxamyl), and organochlorine (lindane) pesticides. Adult Pacific oysters were exposed to several concentrations (0.1,200 ,M) of dichlorvos, carbofuran, and oxamyl for 96 h, and lindane (1.0 and 2.5 ,M) was applied for 12 days. In gill tissues, all pesticides analyzed caused a decrease in AChE activity when compared to the control unexposed group. The mean inhibition concentration (IC50) values were determined for dichlorvos, carbofuran, and oxamyl pesticides. Dichlorvos had the highest toxic effect, with an IC50 of 1.08 ,M; lesser effects were caused by oxamyl and carbofuran, with IC50s of 1.67 and 3.03 ,M, respectively. This study reports the effects of pesticides with several chemical structures and validates measurement of AChE activity in the gill tissues of C. gigas for use in environmental evaluations or food quality tests. © 2009 Wiley Periodicals, Inc. Environ Toxicol 25: 327,332, 2010. [source] Comparing the relative toxicity of malathion and malaoxon in blue catfish Ictalurus furcatusENVIRONMENTAL TOXICOLOGY, Issue 4 2008Winfred G. Aker Abstract Malathion inhibits the critical body enzyme, acetylcholinesterase (AChE). This capability requires that malathion should first be converted to malaoxon to become an active anticholinesterase agent. Conversion can be caused by oxidation in mammals, insects, plants, and in sunlight. In this study, the effects of malathion and malaoxon on catfish Ictalurus furcatus were evaluated. After 96-h exposures, the LC50 (concentration that causes 50% mortality) and IC50 (concentration that causes 50% enzyme inhibition) for malaoxon were lower than corresponding values for malathion. The overall mean 96-h LC50 is 17.0 ppm for malathion and 3.1 ppm for malaoxon. IC50 values for malathion are 8.5 ppm for brain, 10.3 ppm for liver, and 16.6 ppm for muscle. Corresponding values for malaoxon are 2.3, 3.7, and 6.8 ppm, respectively. All the AChE activities in malathion- and malaoxon-exposed catfish brain showed significant inhibition. The oxidation product malaoxon demonstrated higher inhibition on AChE activity than did malathion. Moreover, malaoxon showed significant inhibition on butyrylcholinesterase (BChE) in the liver if the concentrations were increased to more than 1 ppm. Malathion showed no difference between treatment group and control group. Compared with malathion, malaoxon showed higher inhibition on monoamine activity than that of malathion. The results indicated that the oxidative product malaoxon is more toxic than the parent compound malathion. AChE, BChE, and monoamine activities are confirmed as bioindicators of malathion exposure in blue catfish, I. furcatus. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source] Intraclonal variability in Daphnia acetylcholinesterase activity: The implications for its applicability as a biomarkerENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2003Liane Biehl Printes Abstract The relationship between individual growth and acetylcholinesterase (AChE) activity was evaluated for Daphnia magna. Analysis on the influence of two different culture media on baseline AChE activity was performed with Daphnia similis. The results indicated an inverse relationship between D. magna body length and AChE activity. An increase in total protein, which was not proportional to an increase in the rate of the substrate hydrolysis (, absorbance/min), seems to be the reason for this inverse size versus AChE activity relationship. Therefore, toxicants such as phenobarbital, which affect protein and size but not AChE activity directly, have an overall affect on AChE activity. In contrast, the AChE inhibitor parathion altered AChE activity but not protein. Culture medium also had a significant affect on AChE activity in D. similis. Changes in total protein seem to be the main reason for the variations in baseline AChE activity in Daphnia observed in the different evaluations performed in this work. Therefore, AChE activity in Daphnia must be interpreted carefully, and variations related to changes in total protein must be taken into account when applying this enzyme as a biomarker in biological monitoring. [source] Increased toxicity to invertebrates associated with a mixture of atrazine and organophosphate insecticidesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2002Troy D. Anderson Abstract This study examined the joint toxicity of atrazine and three organophosphate (OP) insecticides (chlorpyrifos, methyl parathion, and diazinon) exposed to Hyalella azteca and Musca domestica. A factorial design was used to evaluate the toxicity of binary mixtures in which the lethal concentration/lethal dose (LC1/LD1, LC5/LD5, LC15/LD15, and LC50/LD50) of each OP was combined with atrazine concentrations of 0, 10, 40, 80, and 200 ,g/L for H. azteca and 0, 200, and 2,000 ng/mg for M. domestica. Atrazine concentrations (>40 ,g/L) in combination with each OP caused a significant increase in toxicity to H. azteca compared with the OPs dosed individually. Acetylcholinesterase (AChE) activity also was examined for the individual OPs with and without atrazine treatment. Atrazine in combination with each of the OPs resulted in a significant decrease in AChE activity compared with the OPs dosed individually. In addition, H. azteca that were pretreated with atrazine (>40 ,g/L) were much more sensitive to the OP insecticides compared with H. azteca that were not pretreated with atrazine before being tested. Topical exposure to atrazine concentrations did not significantly increase OP toxicity to M. domestica. The results of this study indicate the potential for increased toxicity in organisms exposed to environmental mixtures. [source] Effects of Anabaena spiroides (cyanobacteria) aqueous extracts on the acetylcholinesterase activity of aquatic speciesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2001José María Monserrat Abstract The effects of aqueous extracts from a cyanobacteria species, Anabaena spiroides, on fish (Odontesthes argentinensis), crab (Callinectes sapidus), and purified eel acetylcholinesterase (AChE) activity were studied. In vitro concentrations of A. spiroides aqueous extract that inhibited 50% of enzyme activity (IC50) were 23.0, 17.2, and 45.0 mg/L of lyophilized cyanobacteria for eel, fish, and crab AChE, respectively. Eel AChE inhibition follows pseudo-first-order kinetics, the same expected for organophosphorus pesticides. Inhibition of purified eel AChE using mixtures of bioxidized malathion and aqueous extract of A. spiroides showed a competitive feature (p < 0.05), suggesting that the toxin(s) could be structurally similar to an organophosphorus pesticide and that toxins present in the aqueous extract inhibit the active site of the enzyme. The inhibition recovery assays using 2-PAM (0.3 mM) showed that (1) bioxidized malathion inhibited 27.0 ± 1.1% of crab and 36.5 ± 0.1% of eel AChE activities; (2) with bioxidized malathion + 2-PAM the registered inhibition was 13.2 ± 2.1% and 3.7 ± 0.5% in crab and eel AChE, respectively; (3) the aqueous extract from A. spiroides inhibited 17.4 ± 2.2% and 59.9 ± 0.5% of crab and eel AChE activity, respectively; and (4) aqueous extract + 2-PAM inhibited 22.3 ± 2.6 and 61.5 ± 0.2% of crab and eel AChEs. The absence of enzyme activity recovery after 2-PAM exposure could imply that the enzyme aging process was extremely quick. [source] Imaging of acetylcholine esterase activity in brainstem nuclei involved in regulation of sleep and wakefulnessEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2007C. Eggers Positron emission tomography with 11C- N -methyl-4-piperidyl-acetate (MP4A) was applied in eight healthy volunteers and two patients with mild Alzheimer's disease (AD) to assess acetylcholine esterase (AChE) activity in magnetic resonance imaging-identified brainstem nuclei. Uptake ratios in lateral dorsal tegmental and pedunculopontine nuclei relative to cerebellum yielded reproducible values for the AChE activity in controls and reduced values in AD, more marked in a patient with complaints of disturbed sleep. Cortical AChE activity was related to the extent of cognitive impairment which was more severe in the AD patient without sleep disturbance. This preliminary observational study demonstrates the feasibility to image and assess AChE activity in small nuclei of the brain stem. This approach may be helpful to investigate the interaction of various nuclei in the complex network regulating sleep and wakefulness in representative patient groups with documented sleep disturbance. [source] Acetylcholinesterase from the invertebrate Ciona intestinalis is capable of assembling into asymmetric forms when co-expressed with vertebrate collagenic tail peptideFEBS JOURNAL, Issue 6 2008Adam Frederick To learn more about the evolution of the cholinesterases (ChEs), acetylcholinesterase (AChE) and butyrylcholinesterase in the vertebrates, we investigated the AChE activity of a deuterostome invertebrate, the urochordate Ciona intestinalis, by expressing in vitro a synthetic recombinant cDNA for the enzyme in COS-7 cells. Evidence from kinetics, pharmacology, molecular biology, and molecular modeling confirms that the enzyme is AChE. Sequence analysis and molecular modeling also indicate that the cDNA codes for the AChET subunit, which should be able to produce all three globular forms of AChE: monomers (G1), dimers (G2), and tetramers (G4), and assemble into asymmetric forms in association with the collagenic subunit collagen Q. Using velocity sedimentation on sucrose gradients, we found that all three of the globular forms are either expressed in cells or secreted into the medium. In cell extracts, amphiphilic monomers (G1a) and non-amphiphilic tetramers (G4na) are found. Amphiphilic dimers (G2a) and non-amphiphilic tetramers (G4na) are secreted into the medium. Co-expression of the catalytic subunit with Rattus norvegicus collagen Q produces the asymmetric A12 form of the enzyme. Collagenase digestion of the A12 AChE produces a lytic G4 form. Notably, only globular forms are present in vivo. This is the first demonstration that an invertebrate AChE is capable of assembling into asymmetric forms. We also performed a phylogenetic analysis of the sequence. We discuss the relevance of our results with respect to the evolution of the ChEs in general, in deuterostome invertebrates, and in chordates including vertebrates. [source] Cardiopulmonary effects of HI-6 treatment in soman intoxicationJOURNAL OF APPLIED TOXICOLOGY, Issue S1 2001A. Göransson-Nyberg Abstract The cardiopulmonary effects of HI-6, together with atropine and soman, were studied in the rat. HI-6 is an effective antidote in acute poisoning with the nerve agent soman. The therapeutic efficiency of HI-6 is still unclear and cannot be explained entirely by the HI-6 reactivating ability of acetylcholinesterase (AChE). Other non-cholinergic factors must be involved. One possible detoxifying process might be an effect of HI-6 on the blood flow to sensitive organs. The purpose of the present study was to investigate 1) whether soman per se induces changes in regional blood flow and 2) whether the blood flow to different organs is affected when HI-6 (50 mg kg,1 i.m.) and atropine (10 mg kg,1 i.m.) are given either before or immediately after soman intoxication (90 µg kg,1 s.c.). For regional blood flow determinations the microsphere method was used with male Wistar rats weighing 300,400 g. The rats were anaesthetised and breathed spontaneously during the experiment. Three different blood flow measurements were made in the same animal and concomitant physiological parameters such as mean arterial blood pressure and respiratory rate were recorded. The blood AChE activity was followed throughout the experiment. Our results show that when HI-6 is given after intoxication with soman, dramatic changes in blood flow occur with a significant decrease in both respiratory rate and blood AChE activity. If HI-6 is given prior to the intoxication, however, all rats are unaffected and none of the parameters measured are changed. Copyright © 2001 John Wiley & Sons, Ltd. [source] The role of thyroid hormone on phenylhydrazine hydrochloride mediated inhibitory effects on blood acetylcholinesterase: An in vivo and in vitro studyJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2002Mitali Banerjee Abstract A novel phenomenon of protective counteraction by thyroid hormone has been demonstrated in phenylhydrazine hydrochloride (PHH) induced insult on blood acetylcholinesterase (AChE, EC 3.1.1.7) activity, in both, in vivo and in vitro conditions. Injection of PHH (20 ,g/g) to juvenile male rats for three consecutive days caused a 48% decrease (p < 0.001) in the total blood AChE activity on the third day (i.e. 24 h after injections for three consecutive days) in comparison to the control animals. Simultaneous injections of thyroxine (T4) 1 or 2 ,g/g with PHH (20 ,g/g) showed a recovery in AChE activity by 27% (p < 0.02) and 55% (p < 0.001), respectively, in comparison to the only PHH-injected animals. T4 at 1, 2 and 4 ,g/g doses showed unchanged levels in comparison to the untreated controls. In our in vitro system, incubations of the RBCs in PHH (2 mM) containing medium also showed an inhibition of 44% (p < 0.001) of the RBC membrane AChE activity in comparison to the control conditions. A recovery of 23,81% of the enzyme activity was observed after simultaneous use of T4 (1 nM,100 nM) or T3 (0.1 nM,100 nM), or triiodothyroacetic acid (TRIAC) (100 nM) with PHH (2 mM) in a dose-dependent manner with a potency profile of T3 > T4 > TRIAC. Incubation of RBCs only with T4, T3, or TRIAC at 0.1,100 nM concentration did not cause any alteration in the membrane AChE activity in comparison to control conditions. Thus, thyroid hormone distinctly demonstrated a counteraction or protective nature of action on the PHH-induced inhibition of total blood and RBC membrane AChE activity. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:162,168, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10039 [source] Altered glycosylation of acetylcholinesterase in Creutzfeldt,Jakob diseaseJOURNAL OF NEUROCHEMISTRY, Issue 1 2006María-Ximena Silveyra Abstract Changes in the glycosylation pattern of brain proteins have been associated with Creutzfeldt,Jakob disease (CJD). We have investigated the glycosylation status of acetylcholinesterase (AChE) by lectin binding assay. Our data show that in lumbar CSF from definite and probable sporadic CJD cases AChE activity is lower compared with that in age-matched controls. We also show, for the first time, that AChE glycosylation is altered in CJD CSF and brain. Unlike Alzheimer's disease, in which an alteration in both the glycosylation and levels of AChE molecular forms is observed, the abnormal glycosylation of AChE in CJD appears to be unrelated to changes in molecular forms of this enzyme. These findings suggest that altered AChE glycosylation in CJD may be a consequence of the general perturbation of the glycosylation machinery that affects prion protein, as well as other proteins. The diagnostic potential of these changes remains to be explored. [source] Abundant Tissue Butyrylcholinesterase and Its Possible Function in the Acetylcholinesterase Knockout MouseJOURNAL OF NEUROCHEMISTRY, Issue 3 2000Bin Li Abstract: We have described recently an acetylcholinesterase (AChE) knockout mouse. While comparing the tissue distribution of AChE and butyrylcholinesterase (BChE), we found that extraction buffers containing Triton X-100 strongly inhibited mouse BChE activity. In contrast, buffers with Tween 20 caused no inhibition of BChE. Conventional techniques grossly underestimated BChE activity by up to 15-fold. In Tween 20 buffer, the intestine, serum, lung, liver, and heart had higher BChE than AChE activity. Only brain had higher AChE than BChE activity in AChE +/+ mice. These findings contradict the dogma, based mainly on observations in Triton X-100 extracts, that BChE is a minor cholinesterase in animal tissues. AChE +/- mice had 50% of normal AChE activity and AChE -/- mice had none, but all mice had similar levels of BChE activity. BChE was inhibited by Triton X-100 in all species tested, except rat and chicken. Inhibition was reversible and competitive with substrate binding. The active site of rat BChE was unique, having an arginine in place of leucine at position 286 (human BChE numbering) in the acyl-binding pocket of the active site, thus explaining the lack of inhibition of rat BChE by Triton X-100. The generally high levels of BChE activity in tissues, including the motor endplate, and the observation that mice live without AChE, suggest that BChE has an essential function in nullizygous mice and probably in wild-type mice as well. [source] Relevant activities of extracts and constituents of animals used in traditional Chinese medicine for central nervous system effects associated with Alzheimer's diseaseJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2006Yuhao Ren The centipede Scolopendra subspinipes mutilans L. Koch (,Wugong'), the beetle Mylabris phalerata Pallas (,Ban mao') and the earthworm Pheretima aspergillum Chen (,DiLong') have a reputation in traditional Chinese medicine for reducing symptoms of central nervous system decline, including memory loss. A series of extracts of all three organisms was tested for acetylcholinesterase (AChE) inhibition and copper ion binding effects, the latter likely to reduce oxidative damage caused by excess copper. The beetle and centipede chloroform extracts showed the strongest AChE inhibitory effects (30.6% inhibition at 105 ,g mL,1 and 32.3% inhibition at 167 ,g mL,1, respectively) and, in the case of the centipede, this was traced to the unsaturated fatty acids present using bioassay-guided fractionation. Cantharidin from the beetle was shown to have AChE activity (31% inhibition at 1 ,M, 0.196,g mL,1), making it a major contributor to the activity of the beetle extract. The earthworm showed no AChE inhibitory activity. Since unsaturated fatty acids have not been previously reported to have AChE inhibitory activity, a series of related compounds was tested to determine structure-activity relationships. It was found that activity existed where there was a chain length of more than 16 C atoms with at least one unsaturated bond in the chain. The carboxylic acid group was also necessary for activity. The fatty acids present in the centipede also showed the ability to bind copper ions when tested using a novel thin layer chromatography method designed to detect copper-binding compounds. The activities reported give some support to the use of the beetle and centipede in traditional Chinese medicine for improving cognitive function. [source] Monitoring a Marine Coastal Area: Use of Mytilus galloprovincialis and Mullus barbatus as BioindicatorsMARINE ECOLOGY, Issue 2002Ilaria Corsi Abstract. Samples of Mytilus galloprovincialis and Mullus barbatus were collected in eight coastal sites along the South Adriatic and Ionic coasts of Italy in spring 2000 for a survey of coastal pollution in the Mediterranean basin. Specimens were analysed using an integrated approach based on residue analysis of common aquatic pollutants like organochlorines such as hexachlorobenzene (HCB), DDTs and polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), heavy metals and nonylphenols (NPnE) and biomarker responses such as acetylcholinesterase (AChE) activity, and the two specific P450 activities benzo(a)pyrene monooxygenase (BPMO) and 7-ethoxyre-sorufin-(9-deethylase (EROD). Biological and morphological parameters like somatic liver index (SLI), gonadosomatic index (GSI) and gonadal and gamete histology (eggs and sperms) were also evaluated in red mullet samples. A contamination gradient in which several hot spots occur were revealed in this study. The hot spots account for high levels of organochlorines in both species near incinerators and of PAHs in harbour areas. Levels of both NPnE and AChE activity were highest in two protected marine areas and were within detectable limits in others. This finding was confirmed by P450 activities, in which maximum levels were detected in harbours and protected marine areas. No morphological alterations of male and female gonads were observed on the histological level. [source] Mechanisms of cholinergic dysfunction in rabbits following recurrent aspiration of cow's milk,PEDIATRIC PULMONOLOGY, Issue 6 2001Gary L. Larsen MD Abstract Recurrent aspiration of cow's milk has been shown to alter neural control of airways in young rabbits (Gelfand et al., 1997). The purpose of this study was to define the mechanisms responsible for in vitro cholinergic hyperresponsiveness in this model. Beginning at 1 week of age, rabbits received either 0.5 mL/kg whole cow's milk or sterile saline intranasally while under light anesthesia. This was repeated each weekday for 2 weeks. At 8 weeks of age, rabbits were sacrificed. Portions of lungs underwent lavage with sterile saline. Tracheal smooth muscle (TSM) segments were also removed. Segments were assessed for acetylcholine (ACh) release by high-performance liquid chromatography ( HPLC) with electrochemical detection or acetylcholinesterase (AChE) kinetic activity by spectrophotometry. Substance P (SP), a neuropeptide that can increase ACh release from nerves, was also assessed using an enzyme immunoassay to define the content in lavage and TSM segments. Immunohistochemistry for SP within airways was also assessed. We found that recurrent aspiration of milk led to statistically significant alterations in many parameters. Acetylcholine release was significantly greater in segments of airways from rabbits that had aspirated cow's milk (27.5,±,1.7 vs. 20.1,±,1.6 pmol/min/g tissue) than saline. At the same time, AChE activity was less in the group that aspirated milk (8.7,±,0.4 vs. 10.2,±,0.5 nmol/min/mg protein) compared to saline. The amount of SP within both lavage as well as tissue homogenates was greater in the group that had aspirated the foreign protein (159.1,±,28.9 vs. 41.9,±,5.2 pmol/mg protein in lavage; 158.7,±,31.9 vs. 80.5,±,7.8 pmol/mg protein in tissues) than saline controls. While total cholinergic nerve density as assessed by choline acetyltransferase was not significantly different between groups, SP-positive immunoreactive nerves were easily identified in the group that aspirated cow's milk. This study suggests that cholinergic hyperresponsiveness caused by repeated aspiration of milk is due to several abnormalities, including prejunctional (increase in ACh release) as well as junctional (decrease in AChE) mechanisms within the airways. In addition, an upregulation of SP within airways is part of this process. Pediatr Pulmonol. 2001; 32:409,417. © 2001 Wiley-Liss, Inc. [source] Acetylcholinesterase inhibitory potential of a carbazole alkaloid, mahanimbine, from Murraya koenigiiPHYTOTHERAPY RESEARCH, Issue 4 2010N. Satheesh Kumar Abstract In the search for acetylcholinesterase (AChE) inhibitors from Indian medicinal plants, via bioassay-guided isolation, a carbazole alkaloid, mahanimbine [3, 5-dimethyl-3-(4- methylpent-3-enyl)-11H-pyrano [5, 6-a] carbazole], was isolated from the petroleum ether extract of the leaves of Murraya koenigii. Inhibition of AChE was evaluated based on Ellman's method using 96-well microplate readers. Mahanimbine inhibited AChE activity in a dose-dependent manner with an IC50 value of 0.03 ± 0.09,mg/mL, while galantamine was used as a standard. The AChE inhibitory activity of this carbazole alkaloid has not been reported so far, and this study is the first to reveal this activity in carbazole alkaloid mahanimbine, isolated from Murraya koenigii. Copyright © 2009 John Wiley & Sons, Ltd. [source] Effects of Xenobiotic Compounds on Cell Activities in Euplotes crassusTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2005FRANCESCA TRIELLI It is now widely accepted that Protists are relevant bioassays to be exploited for the study of environmental modifications due to the presence of xenobiotic compounds. In this work, we evaluated the possibility of utilizing Euplotes crassus, an interstitial marine ciliate, for the pre-chemical screening of environmental sites, such as estuarine and coastal sediments. With this aim, we tested the sensitivity of E. crassus to exposure to three classes of pollutants: an organophosphate neurotoxic drug, basudin, largely used for pest control in agricultural sites, a toxic heavy metal, mercury (HgCl2), and an aromatic polycyclic hydrocarbon, benzopyrene (BP). We found a dose-dependent effect of these compounds on cell viability at concentrations ranging from 1/102 v/v to 1/107 v/v for basudin, from 5 ,M to 0.1 ,M for HgCl2, and from 50 ,M to 1 ,M for BP. In particular, 100% mortality was caused by a 1-h exposure to 1/105 v/v basudin, or 2 ,M HgCl2, or 25 ,M BP, and by a 24-h exposure to 1/106 v/v basudin, 0.5 ,M HgCl2, or 5 ,M BP. A significant decrease in the daily mean fission rate (P<0.001) was found after exposure to 1/107 v/v basudin, or 0.25 ,M HgCl2, or 1 ,M BP. Moreover, as it is well known that the inhibition of acetylcholinesterase (AChE) activity represents a specific biomarker for neurotoxic drugs, we first detected this enzyme activity in E. crassus, using cytochemical, spectrophotometric, and electrophoretic methods; then, AChE activity was characterized by its sensitivity to specific AChE inhibitors and to variations in pH and temperature. Like AChE present in higher organisms, the AChE activity detected in E. crassus was inhibited by exposure to basudin. Conversely, exposure to HgCl2, or PB did not inhibit AChE activity, but caused a significant reduction in lysosomal membrane stability. [source] Sinusoidal ELF magnetic fields affect acetylcholinesterase activity in cerebellum synaptosomal membranesBIOELECTROMAGNETICS, Issue 4 2010Silvia Ravera Abstract The effects of extremely low frequency magnetic fields (ELF-MF) on acetylcholinesterase (AChE) activity of synaptosomal membranes were investigated. Sinusoidal fields with 50,Hz frequency and different amplitudes caused AChE activity to decrease about 27% with a threshold of about 0.74,mT. The decrease in enzymatic activity was independent of the time of permanence in the field and was completely reversible. Identical results were obtained with exposure to static MF of the same amplitudes. Moreover, the inhibitory effects on enzymatic activity are spread over frequency windows with different maximal values at 60, 200, 350, and 475,Hz. When synaptosomal membranes were solubilized with Triton, ELF-MF did not affect AChE activity, suggesting the crucial role of the membrane, as well as the lipid linkage of the enzyme, in determining the conditions for inactivation. The results are discussed in order to give an interpretation at molecular level of the macroscopic effects produced by ELF-MF on biological systems, in particular the alterations of embryo development in many organisms due to acetylcholine accumulation. Bioelectromagnetics 31:270,276, 2010. © 2009 Wiley-Liss, Inc. [source] The experimental Alzheimer drug phenserine: preclinical pharmacokinetics and pharmacodynamicsACTA NEUROLOGICA SCANDINAVICA, Issue 2000N. H. Greig Phenserine, a phenylcarbamate of physostigmine, is a new potent and highly selective acetylcholinesterase (AChE) inhibitor, with a >50-fold activity versus butyrylcholinesterase (BChE), in clinical trials for the treatment of Alzheimer's disease (AD). Compared to physostigmine and tacrine, it is less toxic and robustly enhances cognition in animal models. To determine the time-dependent effects of phenserine on cholinergic function, AChE activity, brain and plasma drug levels and brain extracellular acetylcholine (ACh) concentrations were measured in rats before and after phenserine administration. Additionally, its maximum tolerated dose, compared to physostigmine and tacrine, was determined. Following i.v. dosing, brain drug levels were 10-fold higher than those achieved in plasma, peaked within 5 min and rapidly declined with half-lives of 8.5 and 12.6 min, respectively. In contrast, a high (>70%) and long-lasting inhibition of AChE was achieved (half-life >8.25 h). A comparison between the time-dependent plasma AChE inhibition achieved after similar oral and i.v. doses provided an estimate of oral bioavailability of 100%. Striatal, in vivo microdialysis in conscious, freely-moving phenserine-treated rats demonstrated >3-fold rise in brain ACh levels. Phenserine thus is rapidly absorbed and cleared from the body, but produces a long-lasting stimulation of brain cholinergic function at well tolerated doses and hence has superior properties as a drug candidate for AD. It selectively inhibits AChE, minimizing potential BChE side effects. Its long duration of action, coupled with its short pharmacokinetic half-life, reduces dosing frequency, decreases body drug exposure and minimizes the dependence of drug action on the individual variations of drug metabolism commonly found in the elderly. [source] | ||||||||||||||||