Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malathion-induced marked potentiation of BPMC toxicity (about fivefold) was analyzed by measuring LD50 as an index of acute toxicity. The acute lethality of BPMC was decreased by muscarinic blockers (atropine, methylatropine, or trihexyphenidyl) or a monoamine oxidase inhibior (pargyline) and increased by a monoamine depleter (reserpine) or a dopaminergic blocker (haloperidol). The potentiation observed with BPMC and malathion was decreased by the muscarinic blockers, monoamine depleters (reserpine, alpha-methyl-p-tyrosine), an alpha-noradrenergic blocker (phentolamine), or haloperidol. The acute toxicities of other N-methylcarbamates MPMC (3,4-dimethylphenyl N-methylcarbamate), MTMC (3-methylphenyl N-methylcarbamate), NAC (1-naphthyl N-methylcarbamate), and XMC (3,5-dimethylphenyl N-methylcarbamate) were potentiated by malathion to a lesser degree than that of BPMC. Atropine protected against the lethalities of all N-methylcarbamates. Reserpine or haloperidol potentiated the lethalities of N-methylcarbamates with a similar tendency toward malathion. When the inhibitory effect of each N-methylcarbamate on brain acetylcholinesterase (AChE) was compared with its LD50, among five N-methylcarbamates BPMC had particularly strong anti-AChE activity. This characteristic of BPMC was not observed after the treatment with reserpine. These results suggest that BPMC may act not only on cholinergic nerves as an anti-AChE, but also on monoaminergic nerves which antagonize the lethal cholinergic effect. Malathion might inhibit the effect of BPMC on the monoaminergic nerves, thereby markedly potentiating the lethal effect of BPMC.
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PMID:Contribution of monoaminergic nervous system in potentiation of 2-sec-butylphenyl N-methylcarbamate (BPMC) toxicity by malathion in male mice. 356 12

The genetic associations with the pathological features of AD are diverse: A rapidly growing number of mutations in presenilin 1 and 2 on chromosomes 14 and 1, respectively, are found in many early-onset FAD patients (Lendon et al., 1997). In addition, beta PP mutations are found in a small percentage of early-onset FAD kindreds. The apoE4 allele on chromosome 19 is associated with the presence of the most common form of AD, sporadic AD (Wisniewski & Frangione, 1992; Namba et al., 1991). However, it is clear that other proteins are also involved in the pathogenesis of AD, since some early-onset FAD kindreds do not have linkage to PS1, PS2, apoE, or beta PP, while at least 50% of late-onset AD is unrelated to apoE. Other proteins which have been implicated in the formation of senile plaques, but so far are not known to have any genetic linkage to AD, include proteoglycans (Snow et al., 1987), apoA1 (Wisniewski et al., 1995a), alpha 1-antichymotrypsin (Abraham et al., 1988), HB-GAM (Wisniewski et al., 1996a), complement components (McGeer & Rogers, 1992), acetylcholinesterase (Friede, 1965), and NAC (Ueda et al., 1993). Which of these proteins will be the most important for the etiology of the most common form of AD, late-onset sporadic AD, remains an open question. Three of the genes which are now known to be linked to AD, including PS1, beta PP, and apoE, have been established immunohistochemically and biochemically to be components of senile plaques (see Fig. 1). This raises at least two possibilities: either each of these proteins is part of one pathway with A beta-related amyloid formation as a final causative pathogenic event or amyloid deposition in AD is a reactive process related to dysfunction of a number of different CNS proteins. Whether or not amyloid formation is directly causative in the pathogenesis of AD, current data suggest that new therapeutic approaches which may inhibit the aggregation and/or the conformational change of sA beta to A beta fibrils (Soto et al., 1996) have the greatest likelihood to make a significant impact on controlling amyloid accumulation in AD.
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PMID:Biology of A beta amyloid in Alzheimer's disease. 944 Jan 20

In recent decades, because considerable progress has been made due to rapid developments in basic theory and techniques in molecular biology and immunology, the determination of trace enzyme proteins is not difficult. We measured the serum concentration of Creatine kinase-MB (CK-MB) mitochondria aspartate aminotransferase (m-AST) and cholinesterase (ChE) immunologically and compared these findings with those of an assay of enzyme activity. Purification of enzyme protein and preparation of serum antibodies monoclonal antibodies established the immunological assay methods. Equipment and reagents for enzyme activity test use 7150 Biochemical Analyzer. CK-NAC AST and ChE were produced by trace kits (Australia). CK-MB and m-AST use immunological inhibition method. CK-MB m-AST ChE of protein determination used immunological turbidimetry. The normal group included 150 cases and the 1990 patient group. Results of the two methods did not significantly differ for normal controls, but were significantly different in the patient group. These results demonstrated that the two methods differ, although each may have specific clinical significance. How to evaluate these differences needs to be studied further, but immunological assay uses higher values for clinical diagnosis than enzyme activity assay.
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PMID:[Determination enzyme protein of CK-MB m-AST and ChE by immunological methods and survey of its applying values]. 972 41

Efficacy of thiol chelators viz. N-acetyl cysteine and D-penicillamine (NAC and DPA) along with nutritional supplements viz. zinc acetate, sodium selenite and magnesium sulphate (Zn, Se and Mg) in the treatment of mercury intoxication was investigated in rats. This is of particular interest since high bonding affinity between mercuric ion and the thiol group exits. The mutual antagonism of mercury and selenium is one of the strongest examples of the interaction in the trace element field. Adult rats of Sprague-Dawley strain were administered a bolus dose of dimethyl mercury (10 mg/kg) orally. A significant rise in the aspartate aminotransferase, alanine aminotransferase, serum alkaline phosphatase, lactate dehydrogenase, gamma glutamyltranspeptidase, bilirubin and creatinine were observed. Single mercury exposure also resulted in a significant increase in lipid peroxides with a concomitant decrease in reduced glutathione level in liver, kidney and brain. A decrease in the enzymatic activities of acetyl cholinesterase in different regions of the brain was observed. These parameters were restored considerably with chelating agents along with nutritional supplementation, but NAC+Se and DPA+Mg offered significant protection in comparison with other combinations.
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PMID:Effect of monothiol along with antioxidant against mercury-induced oxidative stress in rat. 1825 9

Chlorpyrifos (CPF) is a neurotoxic organophosphorus (OP) insecticide widely used for agricultural purposes. CPF-mediated neurotoxicity is mainly associated with its anticholinesterase activity, which may lead to a cholinergic syndrome. CPF metabolism generates chlorpyrifos-oxon (CPF-O), which possesses higher anticholinesterase activity and, consequently, plays a major role in the cholinergic syndrome observed after CPF poisoning. Recent lines of evidence have also reported non-cholinergic endpoints of CPF- and CPF-O-induced neurotoxicities, but comparisons on the non-cholinergic toxic properties of CPF and CPF-O are lacking. In this study, we compared the non-cholinergic toxicities displayed by CPF and CPF-O in cultured neuronal cells, with a particular emphasis on their pro-oxidant properties. Using immortalized cells derived from mouse hippocampus (HT22 line, which does present detectable acetylcholinesterase activity), we observed that CPF-O was 5-fold more potent in decreasing cell viability compared with CPF. Atropine, a muscarinic acetylcholine receptor antagonist, protected against acetylcholine (ACh)-induced toxicity but failed to prevent the CPF- and CPF-O-induced cytotoxicities in HT22 cells. CPF or CPF-O exposures significantly decreased the levels of the antioxidant glutathione (GSH); this event preceded the significant decrease in cell viability. Pretreatment with N-acetylcysteine (NAC, a GSH precursor) protected against the cytotoxicity induced by both CPF and CPF-O. The present study indicates that GSH depletion is a non-cholinergic event involved in CPF and CPF-O toxicities. The study also shows that in addition of being a more potent AChE inhibitor, CPF-O is also a more potent pro-oxidant molecule when compared with CPF, highlighting the role of CPF metabolism (bioactivation to CPF-O) in the ensuing non-cholinergic toxicity.
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PMID:Glutathione in Chlorpyrifos-and Chlorpyrifos-Oxon-Induced Toxicity: a Comparative Study Focused on Non-cholinergic Toxicity in HT22 Cells. 3265 42