Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) have been reported after exposure to different pesticides, including organophosphates and paraquat. In this study, we have determined ALA-D in 135 pesticide applicators (sprayers) from an intensive agriculture setting at two periods with different pesticide exposure. Acetylcholinesterase (AChE) was used as a reference biomarker. The effects of the combined polymorphism of enzymes involved in the detoxification of pesticides (paraoxonase (PON1), benzoylcholinesterase (BChE), and glutathione S-transferase (GSTM1 and GSTT1)) on the level of the target erythrocyte enzymes were also studied as biomarkers of individual susceptibility. Sprayers presented significant lower levels of ALA-D and AChE than controls (41.3% and 14.5%, respectively) at the high exposure period. When all biomarkers of individual susceptibility to pesticides were considered at the same time, the GSTT1 null allele determined higher ALA-D and AChE activities at the period of high exposure to pesticides. PON1 R allele in turn determined lower AChE activity at the low exposure period. Null genotype for both GST subclasses (GSTM1 and GSTT1) was found to be the unique independent predictor of pesticide-related symptomatology. Interestingly, sprayers were consistently underrepresented among carriers of "unfavourable" BChE variants. In conclusion, ALA-D appears to be an important biological indicator of pesticide exposure and PON1 and GSTT1 are relevant determinants of susceptibility to chronic pesticide poisoning.
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PMID:Changes in erythrocyte enzymes in humans long-term exposed to pesticides: influence of several markers of individual susceptibility. 1592 24

To assess the effects of exposure to complex mixtures of pesticides in farm workers from two communities from Rio Grande do Sul, Brazil, we evaluated the activities of butyrylcholinesterase (BChE) and delta-aminolevulinic acid dehydratase (ALA-D) enzymes, hematological, lipid parameters, and genotoxicity using two tests to detect DNA damage, the Comet assay in peripheral blood leukocytes and the micronucleus (MN) test in oral mucosa cells. The use of personal protective equipment (PPE), age and smoke habits were considered in the analysis. There was a significant decrease in the BChE and ALA-D activities in farm workers (n=37) relative to the control group (n=20) (P< or =0.05 and P< or =0.001, respectively). The Comet assay in peripheral blood leukocytes showed that the Damage index and Damage frequency observed in the exposed group were significantly higher in relation to the controls (P< or =0.001, and P< or =0.05, respectively). No differences were detected regarding the hematological parameters, lipids profile, and MN frequencies. In addition, no significant differences were observed between younger (< or =38 years) and older subjects (>38 years), or between smokers and non-smokers within the groups, either by Comet assay or MN test. However, the use of PPE seems to be important in the prevention of contamination, as suggested by BChE levels and Comet assay results.
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PMID:Occupational exposure of farm workers to pesticides: biochemical parameters and evaluation of genotoxicity. 1867 10

The expression of recombinant proteins of pharmaceutical interest in the milk of transgenic farm animals can result in phenotypes exhibiting compromised lactation performance, as a result of the extraordinary demand placed on the mammary gland. In this study, we investigated differences in the protein composition of milk from control and transgenic goats expressing recombinant human butyrylcholinesterase. In Experiment 1, the milk was characterized by gel electrophoresis and liquid chromatography/mass spectrometry in order to identify protein bands that were uniquely visible in the transgenic milk and/or at differing band densities compared with controls. Differences in protein content were additionally evaluated by computer assisted band densitometry. Proteins identified in the transgenic milk only included serum proteins (i.e. complement component 3b, ceruloplasmin), a cytoskeleton protein (i.e. actin) and a stress-induced protein (94 kDA glucose-regulated protein). Proteins exhibiting evident differences in band density between the transgenic and control groups included immunoglobulins, serum albumin, beta-lactoglobulin and alpha-lactalbumin. These results were found to be indicative of compromised epithelial tight junctions, premature mammary cell death, and protein synthesis stress resulting from transgene expression. In Experiment 2, the concentration of alpha-lactalbumin was determined using the IDRing assay and was found to be significantly reduced on day 1 of lactation in transgenic goats (4.33 +/- 0.97 vs. 2.24 +/- 0.25 mg/ml, P < 0.01), but was not different from non-transgenic controls by day 30 (0.99 +/- 0.46 vs. 0.90 +/- 0.11 mg/ml, P > 0.05). We concluded that a decreased/delayed expression of the alpha-lactalbumin gene may be the cause for the delayed start of milk production observed in this herd of transgenic goats.
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PMID:Protein profile and alpha-lactalbumin concentration in the milk of standard and transgenic goats expressing recombinant human butyrylcholinesterase. 1929 33

In this study, we examined the effects of low levels and sub-chronic exposure to methylmercury (MeHg) on butyrylcholinesterase (BuChE) activity in rats. Moreover, we examined the relationship between BuChE activity and oxidative stress biomarkers [delta-aminolevulinic acid dehydratase (delta-ALA-D) and malondialdehyde levels (MDA)] in the same animals. Rats were separated into three groups (eight animals per group): (Group I) received water by gavage; (Group II) received MeHg (30 microg/kg/day) by gavage; (Group III) received MeHg (100 microg/kg/day). The time of exposure was 90 days. BuChE and ALA-D activities were measured in serum and blood, respectively; whereas MDA levels were measured in plasma. We found BuChE and ALA-D activities decreased in groups II and III compared to the control group. Moreover, we found an interesting negative correlation between plasmatic BuChE activity and MDA (r = -0.85; p < 0.01) and a positive correlation between plasmatic BuChE activity and ALA-D activities (r = 0.78; p < 0.01), thus suggesting a possible relationship between oxidative damage promoted by MeHg exposure and the decrease of BuChE activity. In conclusion, long-term exposure to low doses of MeHg decreases plasmatic BuChE activity. Moreover, the decrease in the enzyme is strongly correlated with the oxidative stress promoted by the metal exposure. This preliminary finding highlights a possible mechanism for MeHg to reduce BuChE activity in plasma. Additionally, this enzyme could be an auxiliary biomarker on the evaluation of MeHg exposure.
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PMID:Sub-chronic exposure to methylmercury at low levels decreases butyrylcholinesterase activity in rats. 1987 86

Organophosphates (OPs), which are widely used as pesticides, are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The inactivation of AChE results in the accumulation of acetylcholine at cholinergic receptor sites, causing a cholinergic crisis that can lead to death. The classical treatment for OP poisoning is administration of oximes, but these compounds are ineffective in some cases. Here we determined whether the new compound isatin-3-N(4)-benzilthiosemicarbazone (IBTC), which in our previous study proved to be an antioxidant and antiatherogenic molecule, could protect and reactivate AChE and BChE. Toxicity of IBTC after subcutaneous injection in mice was measured using assays for oxidized diclorofluoresceine (DCF), thiobarbituric acid reactive substances (TBARS), non-protein thiol (NPSH) levels, and catalase (CAT), sodium potassium (Na(+)/K(+)) ATPase, delta-aminolevulinic acid dehydratase (ALA-D), and glutathione peroxidases (GPx) enzyme activities. The cytotoxicity was evaluated and the enzymatic activity of cholinesterase was measured in human blood samples. Molecular docking was used to predict the mechanism of IBTC interactions with the AChE active site. We found that IBTC did not increase the amount of DCF-RS or TBARS, did not reduce NPSH levels, and did not increase CAT, (Na(+)/K(+)) ATPase, ALA-D, or GPx activities. IBTC protected and reactivated both AChE and BChE activities. Molecular docking predicted that IBTC is positioned at the peripheral anionic site and in the acyl binding pocket of AChE and can interact with methamidophos, releasing the enzyme's active site. Our results suggest that IBTC, besides being an antioxidant and a promising antiatherogenic agent, is a non-toxic molecule for methamidophos poisoning treatment.
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PMID:Isatin-3-N4-benzilthiosemicarbazone, a non-toxic thiosemicarbazone derivative, protects and reactivates rat and human cholinesterases inhibited by methamidophos in vitro and in silico. 2254 56

Previously we reported that intensive agriculture workers exposed to pesticides had decreased levels of the intraerythrocyte enzymes delta-9-aminolevulinic acid dehydratase (ALA-D) and superoxide dismutase (SOD), very likely as a result of pesticide-induced oxidative stress. We have now examined in this population potential gene-environment interactions by modeling generalized estimating equations (GEE) adjusted for age, sex, body mass index and tobacco and alcohol consumption. Particularly, we assessed the interaction effects between plasma and erythrocyte cholinesterases (BChE and AChE, used as proxies for short- and long-term pesticide exposure, respectively) and a number of genetic polymorphisms of pesticide metabolizing enzymes such as paraoxonase-1 (PON1), glutathione-S-transferases (GST) and plasma cholinesterase variants (BCHE) on levels of erythrocyte antioxidant enzymes (SOD, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase and ALA-D). We observed significant interaction effects between BChE activity and PON1192R allele on catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase activities. BChE also interacted significantly with GSM1 null genotype on ALA-D and SOD. Regarding long-term pesticide exposure, a significant interaction was found between AChE and genotypes PON1192QR and PON1108CC on GR; between AChE and PON1192RR on SOD, and between AChE and GSTM1, GSTT1 and unusual BCHE variants on catalase activity. These findings suggest relevant gene-pesticide interactions and highlight the potential role of genetic risk factors in the pathomechanism of oxidative stress-induced degenerative diseases following pesticide exposure.
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PMID:Evaluation of pesticide-induced oxidative stress from a gene-environment interaction perspective. 2303 75