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)

Two acetylcholinesterases (AChEs), AChE1 and AChE2, differing in substrate specificity and in some aspects of inhibitor sensitivity, have been characterized in the mosquito Culex pipiens. The results of ultracentrifugation in sucrose gradients and nondenaturing gel electrophoresis of AChE activity peak fractions show that each AChE is present as two molecular forms: one amphiphilic dimer possessing a glycolipid anchor and one hydrophilic dimer that does not interact with nondenaturing detergents. Treatment by phosphatidylinositol-specific phospholipase C converts each type of amphiphilic dimer into the corresponding hydrophilic dimer. Molecular forms of AChE1 have a lower electrophoretic mobility than those of AChE2. However, amphiphilic dimers and hydrophilic dimers have similar sedimentation coefficients (5.5S and 6.5S, respectively). AChE1 and AChE2 dimers, amphiphilic or hydrophilic, resist dithiothreitol reduction under conditions that allow reduction of Drosophila AChE dimers. In the insecticide-susceptible strain S-LAB, AChE1 is inhibited by 5 x 10(-4) M propoxur (a carbamate insecticide), whereas AChE2 is resistant. All animals are killed by this concentration of propoxur, indicating that only AChE1 fulfills the physiological function of neurotransmitter hydrolysis at synapses. In the insecticide-resistant strain, MSE, there is no mortality after exposure to 5 x 10(-4) M propoxur: AChE2 sensitivity to propoxur is unchanged, whereas AChE1 is now resistant to 5 x 10(-4) M propoxur. The possibility that AChE1 and AChE2 are products of tissue-specific posttranslational modifications of a single gene is discussed, but we suggest, based on recent results obtained at the molecular level in mosquitoes, that they are encoded by two different genes.
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PMID:Existence of two acetylcholinesterases in the mosquito Culex pipiens (Diptera:Culicidae). 886 21

Resistance mechanisms of a strain (PRAIAS) of northern house mosquito, Culex pipiens L., collected in Portugal in 1993, and highly resistant to organophosphates and carbamates, were investigated by comparing the resistance characteristics to 3 organophosphorous (temephos, chlorpyrifos, malathion) and 1 carbamate (propoxur) insecticides in the presence or absence of synergists; and by determining the possible occurrence of overproduced esterases or insensitive acetylcholinesterase (AChE). The reference strain MSE from southern France, with an insensitive AChE, was included in all analyses for comparison. For organophosphorous insecticides, resistance in PRAIAS was caused by an insensitive AChE and an increase in oxidative metabolism, although the 2nd mechanism has only a marginal effect. For propoxur, the insensitive AChE was the only resistance mechanism detected. Biochemical properties of both the French and Portuguese insensitive AChEs were similar. We cannot exclude the possibility that PRAIAS and MSE strains possess exactly the same insensitive AChE allele.
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PMID:An insensitive acetylcholinesterase in Culex pipiens (Diptera:Culicidae) from Portugal. 891 10

We examined the effects of organophosphate exposure on mRNA expression levels of synaptic- and target tissue-specific proteins in rats. We treated rats with a single dose of Disulfoton (O,O-diethyl S-2-ethylthioethyl phosphorodithioate) and used quantitative reverse transcription-polymerase chain reaction (RT-PCR) to measure the time course of changes in the levels of mRNAs encoding acetylcholinesterase (AChE), nicotinic acetylcholine receptor (nAChR), beta-enolase (MSE), and gamma-enolase (NSE) in soleus muscles and sciatic nerves. The expression levels of synaptic genes encoding AChE in both tissues were significantly decreased, with a nadir at 12h after the administration, and this down-regulation lasted for up to 30 days after administration. Similarly, the level of nAChR mRNA in soleus muscle also decreased, with a nadir at 48 h after administration and a return to 95% of that of the control levels by 30 days after administration. These results indicate that administration of organophosphate can decrease AChE and nAChR expression in the neuromuscular junction, and are suggestive of multiple mechanisms of down-regulation of both AChE and nAChR, some of which might involve alterations at the transcriptional level. The transcript level of the target tissue-specific gene encoding MSE in soleus muscle was slightly decreased, with a nadir at 48 h after administration, and was still lower than that of the control level after 30 days. In contrast, the level of the NSE transcript in sciatic nerve significantly increased within 2 h, and this up-regulation was sustained until 30 days after administration. Although the functions of either of these enolases are not completely established, up-regulation of NSE mRNA may be a marker for the nervous system abnormality following organophosphate exposure. All of these phenomena may contribute to the long-lasting neurotoxic effects observed after developmental exposure to organophosphates.
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PMID:Changes in mRNA expression levels of synaptic- and target tissue-specific proteins after organophosphate exposure. 1293 43