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| O LockridgeSummaryAffiliation: University of Nebraska Medical Center Country: USA Publications
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DNA sequence of butyrylcholinesterase from the rat: expression of the protein and characterization of the properties of rat butyrylcholinesteraseAndreea Ticu Boeck
Eppley Institute, 986805, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Biochem Pharmacol 63:2101-10. 2002..3hr. Human serum contains 5mg/L of BChE and 0.01mg/L of AChE. Male rat serum contains 0.2mg/L of BChE and approximately 0.2mg/L of AChE...- Rescue of the acetylcholinesterase knockout mouse by feeding a liquid diet; phenotype of the adult acetylcholinesterase deficient mouseEllen G Duysen
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Brain Res Dev Brain Res 137:43-54. 2002..These findings support the classical role for AChE in nerve impulse conduction and further suggest that AChE is essential for timely physical development and higher brain function... - Pesticides and susceptible populations: people with butyrylcholinesterase genetic variants may be at riskO Lockridge
University of Nebraska Medical Center, Eppley Institute, Omaha 68198 6805, USA
Neurotoxicology 21:113-26. 2000..More studies are needed to strengthen the hypothesis that people with genetic variants of BChE are at higher risk of intoxication from pesticides... 
Review of tyrosine and lysine as new motifs for organophosphate binding to proteins that have no active site serineOksana Lockridge
Eppley Institute, 985950 University of Nebraska Medical Center, Omaha, NE 68198 5950, United States
Chem Biol Interact 187:344-8. 2010..Treatment of neurodegenerative disorders could be developed by identifying methods to reverse OP binding to tyrosine...- A single amino acid substitution, Gly117His, confers phosphotriesterase (organophosphorus acid anhydride hydrolase) activity on human butyrylcholinesteraseO Lockridge
Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
Biochemistry 36:786-95. 1997..Echothiophate and paraoxon were hydrolyzed with the same kcat of 0.75 min-1. This calculates to a rate acceleration of 100,000-fold for hydrolysis of echothiophate and paraoxon by the G117H mutant compared to the nonenzymatic rate... - Tryptophan residue(s) as major components of the human serum paraoxonase active siteD Josse
Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
Chem Biol Interact 119:79-84. 1999..Trp residue(s) may be involved in the binding of aromatic substrates... - Importance of aspartate-70 in organophosphate inhibition, oxime re-activation and aging of human butyrylcholinesteraseP Masson
Centre de Recherches du Service de Sante des Armees, Unite de Biochimie, BP 87, 38702 La Tronche Cedex, France and Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Biochem J 325:53-61. 1997..People with the D70G mutation will be resistant to re-activation of their inhibited BuChE by 2-PAM, but this will be offset by the lower rate of irreversible aging of inhibited BuChE, allowing some regeneration by spontaneous hydrolysis... - Human serum paraoxonase (PON1): identification of essential amino acid residues by group-selective labelling and site-directed mutagenesisD Josse
Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
Chem Biol Interact 119:71-8. 1999..However, we cannot rule out that the effects of mutations on catalytic properties resulted from a remote conformational change and/or misfolding of mutant proteins... - Mass spectrometry identifies multiple organophosphorylated sites on tubulinHasmik Grigoryan
University of Nebraska Medical Center, Eppley Institute for Cancer Research, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
Toxicol Appl Pharmacol 240:149-58. 2009..In conclusion seventeen tyrosines in tubulin have the potential to covalently bind chlorpyrifos oxon. These results will be useful when searching for OP-labeled tubulin in live animals... - Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasmaBin Li
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198 6805, USA
Biochem Pharmacol 70:1673-84. 2005..Since human plasma contains no carboxylesterase, only BChE, PON1, and albumin esterases need to be considered when evaluating hydrolysis of an ester drug in human plasma... - Pseudo-esterase activity of human albumin: slow turnover on tyrosine 411 and stable acetylation of 82 residues including 59 lysinesOksana Lockridge
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
J Biol Chem 283:22582-90. 2008..Acetylated lysines formed adducts that were even more stable. In conclusion, the pseudo-esterase activity of albumin is the result of irreversible acetylation of 82 residues and is not the result of turnover... - Albumin, a new biomarker of organophosphorus toxicant exposure, identified by mass spectrometryEric S Peeples
University of Nebraska Medical Center, Eppley Institute, Omaha, Nebraska 68198-6805, USA
Toxicol Sci 83:303-12. 2005..Carboxylesterase is not a biomarker in man because humans have no carboxylesterase in blood. It is concluded that OP bound to albumin could serve as a new biomarker of OP exposure in man... - Mass spectrometry identifies covalent binding of soman, sarin, chlorpyrifos oxon, diisopropyl fluorophosphate, and FP-biotin to tyrosines on tubulin: a potential mechanism of long term toxicity by organophosphorus agentsHasmik Grigoryan
Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
Chem Biol Interact 175:180-6. 2008..It is concluded that OP bind covalently to tubulin, and that this binding could explain cognitive impairment associated with OP exposure... - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay for organophosphorus toxicants bound to human albumin at Tyr411Bin Li
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA
Anal Biochem 361:263-72. 2007..Our results show that OP pesticides and nerve agents bind covalently to human albumin at Tyr411. The presence of Tyr411 on an exposed surface of albumin suggests that an antibody response could be generated against OP-albumin adducts... - Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesteraseLiya R Mikami
aDepartment of Genetics, Federal University of Parana, Curitiba, Parana, Brasil bEppley Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA
Pharmacogenet Genomics 17:681-5. 2007..BChE genotyping may become important for estimating prognosis, and the knowledge of the genetic variants of BChE in a particular population may be useful for carrying out the genotyping assays... - Mice treated with chlorpyrifos or chlorpyrifos oxon have organophosphorylated tubulin in the brain and disrupted microtubule structures, suggesting a role for tubulin in neurotoxicity associated with exposure to organophosphorus agentsWei Jiang
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 5950, USA
Toxicol Sci 115:183-93. 2010..Covalent binding of CPO to tubulin and to tubulin-associated proteins is a potential mechanism of neurotoxicity... - Wild-type and A328W mutant human butyrylcholinesterase tetramers expressed in Chinese hamster ovary cells have a 16-hour half-life in the circulation and protect mice from cocaine toxicityEllen G Duysen
Eppley Institute, University of Nebraska Medical Center, 986806 Nebraska Medical Center, Omaha, NE 68198 6805, USA
J Pharmacol Exp Ther 302:751-8. 2002..8 units/g i.p. reduced cocaine-induced locomotor activity by 50 and 80%. These results indicate that recombinant human BChE could be useful for treating cocaine toxicity in humans... - Mass spectral characterization of organophosphate-labeled lysine in peptidesHasmik Grigoryan
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA
Anal Biochem 394:92-100. 2009..0, 181.2, and 83.8amu. This new OP-binding motif to lysine suggests new directions to search for mechanisms of long-term effects of OP exposure and in the search for biomarkers of OP exposure... - Role of water in aging of human butyrylcholinesterase inhibited by echothiophate: the crystal structure suggests two alternative mechanisms of agingFlorian Nachon
The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
Biochemistry 44:1154-62. 2005..Pesticides and certain stereoisomers of nerve agents are expected to undergo aging by breaking the P-O bond... - Determination of the DNA sequences of acetylcholinesterase and butyrylcholinesterase from cat and demonstration of the existence of both in cat plasmaC F Bartels
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Biochem Pharmacol 60:479-87. 2000..In addition, a polymorphism in intron 3 of the human ACHE gene was detected, as well as a silent polymorphism at Y116 of the cat ACHE gene... 
Whole body and tissue imaging of the butyrylcholinesterase knockout mouse injected with near infrared dye labeled butyrylcholinesteraseEllen G Duysen
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198 6805, USA
Chem Biol Interact 175:119-24. 2008..It is concluded that the tetrameric BChE glycoprotein of 340 kDa diffuses from the muscle injection site to blood and peripheral organs and has a longer residence time in the organs than in blood...- A collaborative endeavor to design cholinesterase-based catalytic scavengers against toxic organophosphorus estersPatrick Masson
Toxicology Department, Enzymology Unit, Centre de Recherches du Service de Sante des Armees, La Tronche Cedex, France
Chem Biol Interact 175:273-80. 2008..Additional mutations were made for optimizing activity of the new dyad. It is anticipated that these new mutants will have OP hydrolase activity... - Characteristic mass spectral fragments of the organophosphorus agent FP-biotin and FP-biotinylated peptides from trypsin and bovine albumin (Tyr410)Lawrence M Schopfer
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198, USA
Anal Biochem 345:122-32. 2005..This latter result confirms that the organophosphorus binding site of albumin is a tyrosine. This method can be used to search for new biomarkers of organophosphorus agent exposure... - Sensitivity of butyrylcholinesterase knockout mice to (--)-huperzine A and donepezil suggests humans with butyrylcholinesterase deficiency may not tolerate these Alzheimer's disease drugs and indicates butyrylcholinesterase function in neurotransmissionEllen G Duysen
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Toxicology 233:60-9. 2007..Thus, BChE has a function in neurotransmission. People with BChE deficiency are expected to be intolerant of standard doses of the anti-Alzheimer's drugs, (--)-huperzine A and donepezil... - The butyrylcholinesterase knockout mouse is obese on a high-fat dietBin Li
Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
Chem Biol Interact 175:88-91. 2008..Their obesity was not explained by increased levels of octanoyl-ghrelin, or by increased caloric intake, or by decreased exercise. Instead, a role for BChE in fat utilization was suggested... - Reaction kinetics of biotinylated organophosphorus toxicant, FP-biotin, with human acetylcholinesterase and human butyrylcholinesteraseLawrence M Schopfer
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
Chem Res Toxicol 18:747-54. 2005..The binding affinity was estimated to be >85 nM for AChE and >5.8 nM for BChE. It was concluded that FP-biotin is a potent OP, well-suited for searching for new biomarkers of OP exposure... - Kinetic analysis of effector modulation of butyrylcholinesterase-catalysed hydrolysis of acetanilides and homologous estersPatrick Masson
Unite d Enzymologie, Departement de Toxicologie, Centre de Recherches du Service de Sante des Armees, La Tronche Cedex, France
FEBS J 275:2617-31. 2008..The complex inhibition/activation effects of effectors, depending on the integrity of the peripheral anionic site, reflect the allosteric 'cross-talk' between the peripheral anionic site and the catalytic centre... - Hysteresis of butyrylcholinesterase in the approach to steady-state kineticsPatrick Masson
Centre de Recherches du Service de Sante des Armees, BP 87, 38702 La Tronche Cedex, France
Chem Biol Interact 157:143-52. 2005..Therefore, a physiological or toxicological relevance for the hysteresis in BChE cannot be ruled out... - Markers of organophosphate exposure in human serumStacy Wieseler
University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
J Mol Neurosci 30:93-4. 2006..Following this step, identifying the remaining proteins is simply a matter of labeling the proteins with an OP, separating the labeled from nonlabeled proteins, and using Q-trap mass spectrometry for identification... - Development of diagnostics in the search for an explanation of aerotoxic syndromeLawrence M Schopfer
Eppley Institute, University of Nebraska Medical Center, Omaha, 68198, USA
Anal Biochem 404:64-74. 2010..It is concluded that toxic gases or oil mists in cabin air may form adducts on plasma butyrylcholinesterase and albumin, detectable by mass spectrometry... - Hydrolysis of oxo- and thio-esters by human butyrylcholinesterasePatrick Masson
Centre de Recherches du Service de Sante des Armees, Unite d Enzymologie, BP 87, 38702 La Tronche Cedex, France
Biochim Biophys Acta 1774:16-34. 2007..Interaction of these groups with the ethereal hetero-atom can have a neutral, an additive or an antagonistic effect on transition state stabilization, depending on their molecular structure, size and enantiomeric configuration... - Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behaviorPatrick Masson
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 5950, USA
Arch Biochem Biophys 494:107-20. 2010..It is proposed, but not yet proven, that low dose exposure involves OP modification of proteins that have no active site serine... - Mass spectral characterization of organophosphate-labeled, tyrosine-containing peptides: characteristic mass fragments and a new binding motif for organophosphatesLawrence M Schopfer
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
J Chromatogr B Analyt Technol Biomed Life Sci 878:1297-311. 2010..Modified peptides are difficult to find when the OP bears no radiolabel and no tag. The characteristic MSMS fragment ions are valuable because they are identifiers for OP-tyrosine, independent of the peptide... - Structural approach to the aging of phosphylated cholinesterasesPatrick Masson
Centre de Recherches du Service de Sante des Armees, Dept Toxicology, 38702 La Tronche Cedex, France
Chem Biol Interact 187:157-62. 2010..Knowledge of the molecular basis of aging will help to design reactivators of aged ChEs, molecules capable of slowing the aging process, and pseudocatalytic ChE-based bioscavengers... - Nanoimages show disruption of tubulin polymerization by chlorpyrifos oxon: implications for neurotoxicityHasmik Grigoryan
University of Nebraska Medical Center, Eppley Institute for Cancer Research, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
Toxicol Appl Pharmacol 240:143-8. 2009..In conclusion, chlorpyrifos oxon binding to tubulin disrupts tubulin polymerization. These results may lead to an understanding of the neurotoxicity of organophosphorus agents... - Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serineHasmik Grigoryan
Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, United States
Chem Biol Interact 180:492-8. 2009..Another application is in the search for biomarkers of organophosphorus agent exposure. Previous searches have been limited to serine hydrolases. Now proteins such as albumin and keratin can be considered... - The butyrylcholinesterase knockout mouse a research tool in the study of drug sensitivity, bio-distribution, obesity and Alzheimer's diseaseEllen G Duysen
Researcher Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Expert Opin Drug Metab Toxicol 5:523-8. 2009..Knowledge of drug sensitivities in the mouse model of human BChE deficiency will aid in understanding adverse drug effects in humans... - Carbofuran poisoning detected by mass spectrometry of butyrylcholinesterase adduct in human serumHe Li
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA
J Appl Toxicol 29:149-55. 2009..The method uses 1 ml of serum and detects low-level exposure associated with as little as 20% inhibition of plasma butyrylcholinesterase... - Phenotype comparison of three acetylcholinesterase knockout strainsEllen G Duysen
University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
J Mol Neurosci 30:91-2. 2006..AChE-/- mice in strains C57 and CD1died during seizures before postnatal day (P) 21, whereas mice in strain 129/Sv lived to adulthood... - Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometryHe Li
Eppley Institute and Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
Toxicol Sci 100:136-45. 2007..e., the classical X-R scission pathway. In contrast, isomalathion aged through both X-R and P-X pathways; the main aged product resulted from P-S bond cleavage and a minor product resulted from O-C and/or S-C bond cleavage... - Adenovirus-mediated human paraoxonase1 gene transfer to provide protection against the toxicity of the organophosphorus pesticide toxicant diazoxonE G Duysen
Eppley Institute, University of Nebraska Medical Center, Omaha, NE, USA
Gene Ther 18:250-7. 2011..In contrast, none of the three mice in the control group survived one 2LD(50) dose. These results show that hPON1 in mice functions as a prophylactic and offers significant protection against lethal doses of diazoxon... - Conserved aromatic residues of the C-terminus of human butyrylcholinesterase mediate the association of tetramersC V Altamirano
Department of Biochemistry and Molecular Biology, Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
Biochemistry 38:13414-22. 1999.... - Binding and hydrolysis of soman by human serum albuminBin Li
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198 6805, USA
Chem Res Toxicol 21:421-31. 2008..Soman-albumin adducts detected by mass spectrometry could be useful for the diagnosis of soman exposure... - Naturally occurring mutation, Asp70his, in human butyrylcholinesteraseAndreea Ticu Boeck
University of Nebraska Medical Center, Eppley Institute, Omaha, Nebraska 68198-6805, USA
Ann Clin Biochem 39:154-6. 2002..CONCLUSION: People homozygous for the Asp70His mutation are expected to have prolonged apnoea in response to succinylcholine or mivacurium, similar to people with the Asp70Gly mutation... - Gene transfer of acetylcholinesterase protects the knockout mouse from the toxicity of DFPBin Li
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198 6805, USA
J Mol Neurosci 30:79-80. 2006..We used the AChE-/- mouse for these studies because this mouse has no endogenous AChE activity (Xie et al., 2000). Any AChE activity found in tissues could only come from the viral vector... - Five tyrosines and two serines in human albumin are labeled by the organophosphorus agent FP-biotinShi Jian Ding
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
Chem Res Toxicol 21:1787-94. 2008..Diethoxyphosphate-labeled Tyr 411 was stable for months at pH 7.4. These results will be useful in the development of specific antibodies to detect OP exposure and to engineer albumin for use as an OP scavenger... - Resistance to organophosphorus agent toxicity in transgenic mice expressing the G117H mutant of human butyrylcholinesteraseYuxia Wang
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198 6805, USA
Toxicol Appl Pharmacol 196:356-66. 2004..In conclusion, the transgenic G117H BChE mouse demonstrates the factors required to achieve protection from OP toxicity in a vertebrate animal... - Tyrosines of human and mouse transferrin covalently labeled by organophosphorus agents: a new motif for binding to proteins that have no active site serineBin Li
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
Toxicol Sci 107:144-55. 2009..The extent to which tyrosine modification by OP can occur in vivo and the toxicological implications of such modifications require further investigation... - Screening assays for cholinesterases resistant to inhibition by organophosphorus toxicantsYuxia Wang
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198-6805, USA
Anal Biochem 329:131-8. 2004..Both wild-type and G117H BChE were in the epithelial cells of the villi. These assays can be used to identify OP-resistant cholinesterases in culture medium and in animal tissues... - Lamellipodin proline rich peptides associated with native plasma butyrylcholinesterase tetramersHe Li
Eppley Institute and Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Biochem J 411:425-32. 2008..We propose that the proline-rich peptides organize the 4 subunits of BChE into a 340 kDa tetramer, by interacting with the C-terminal BChE tetramerization domain... - Regulation of muscarinic acetylcholine receptor function in acetylcholinesterase knockout miceBin Li
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198, USA
Pharmacol Biochem Behav 74:977-86. 2003..However, mRNA levels for muscarinic receptors were unchanged. These results indicate that one adaptation to the absence of AChE is downregulation of muscarinic receptors, thus reducing response to cholinergic stimulation... - Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene accounts for YT blood group polymorphismC F Bartels
Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805
Am J Hum Genet 52:928-36. 1993..Two additional point mutations in the acetylcholinesterase gene do not affect the amino acid sequence of the mature enzyme... - Crystallization and X-ray structure of full-length recombinant human butyrylcholinesteraseMichelle N Ngamelue
Pathology and Microbiology Department, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198 6495, USA
Acta Crystallogr Sect F Struct Biol Cryst Commun 63:723-7. 2007..Towards these ends, full-length monomeric recombinant BChE has been crystallized for the first time. A 2.8 A X-ray structure was solved in space group P42(1)2, with unit-cell parameters a = b = 156, c = 146 A... - Delivery of human acetylcholinesterase by adeno-associated virus to the acetylcholinesterase knockout mouseAnna Hrabovska
Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
Chem Biol Interact 157:71-8. 2005..This supports the hypothesis that their seizures are induced by excess acetylcholine... - Identification of organophosphate-reactive proteins by tandem mass spectrometryHe Li
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-18105, USA
Chem Biol Interact 157:383-4. 2005 - Intrathecal delivery of fluorescent labeled butyrylcholinesterase to the brains of butyrylcholinesterase knock-out mice: visualization and quantification of enzyme distribution in the brainNoel D Johnson
Division of Comparative Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
Neurotoxicology 30:386-92. 2009..This procedure proved to be an efficient, safe and rapid method to deliver BChE to the CNS of mice, providing a research tool for determining neural protection by BChE following OP exposure... - Increased hepatotoxicity and cardiac fibrosis in cocaine-treated butyrylcholinesterase knockout miceEllen G Duysen
Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
Basic Clin Pharmacol Toxicol 103:514-21. 2008..The observed functional changes following acute high-dose and chronic low-dose cocaine in BChE-/- and +/- mice warrants further investigation into the possibility of increased cocaine toxicity in human beings with BChE deficiency... - Production of the butyrylcholinesterase knockout mouseBin Li
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198 6805, USA
J Mol Neurosci 30:193-5. 2006..The BChE knockout mouse will allow us to test the hypothesis that the function of BChE is to detoxify poisons and will allow us to test the role of BChE in other physiological functions... - Protection from the toxicity of diisopropylfluorophosphate by adeno-associated virus expressing acetylcholinesteraseBin Li
Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA
Toxicol Appl Pharmacol 214:152-65. 2006..We conclude that AChE scavenged OP and in this way protected the activity of butyrylcholinesterase (BChE, EC 3.1.1.8) in motor endplates... - Fast affinity purification coupled with mass spectrometry for identifying organophosphate labeled plasma butyrylcholinesteraseHe Li
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
Chem Biol Interact 175:68-72. 2008..The 29 residue active site tryptic peptide labeled with the nerve agents soman or sarin was identified... - The butyrylcholinesterase knockout mouse as a model for human butyrylcholinesterase deficiencyBin Li
Eppley Institute, 986805, Nebraska Medical Center, Omaha, NE 68198 6805, USA
J Pharmacol Exp Ther 324:1146-54. 2008..p., induced tonicclonic convulsions and death in BChE(-/-) mice. This suggests that butyrylcholine, like pilocarpine, binds to muscarinic receptors. In conclusion, the BChE(-/-) mouse is a suitable model for human BChE deficiency... - The active site of human paraoxonase (PON1)D Josse
University of Nebraska Medical Center, Eppley Institute, Omaha, NE 68198-6805, USA
J Appl Toxicol 21:S7-11. 2001..Fluorescence of PON1 complexed to terbium ion shows that at least one tryptophan is close to the calcium binding site... - Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesteraseW Xie
Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
J Pharmacol Exp Ther 293:896-902. 2000..These findings indicate that butyrylcholinesterase and possibly other enzymes are capable of compensating for some functions of AChE and that the inhibition of targets other than AChE by organophosphorus agents results in death... - Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouseB Li
Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
J Neurochem 75:1320-31. 2000..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... - Early weaning and culling eradicated Helicobacter hepaticus from an acetylcholinesterase knockout 129S6/SvEvTac mouse colonyEllen Gail Duysen
Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
Comp Med 52:461-6. 2002..It is concluded that the non-coprophagic behavior of AChE -/- mice accounts for a low infection rate and that the combination of early weaning, routine testing, and culling provide an effective method for eradication of H. hepaticus... - Reaction of human albumin with aspirin in vitro: mass spectrometric identification of acetylated lysines 199, 402, 519, and 545Mariya S Liyasova
University of Nebraska Medical Center, Department of Environmental, Agricultural and Occupational Health, Omaha, NE 68198 6805, USA
Biochem Pharmacol 79:784-91. 2010..It was concluded that the aspirin esterase activity of albumin is a pseudo-esterase activity in which aspirin stably acetylates lysines and releases salicylate... - Detection of adduct on tyrosine 411 of albumin in humans poisoned by dichlorvosBin Li
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 5950, USA
Toxicol Sci 116:23-31. 2010..Identification of other OP-modified proteins may lead to an understanding of neurotoxic symptoms that appear long after the initial OP exposure... - Knockout of one acetylcholinesterase allele in the mouseW Xie
Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
Chem Biol Interact 119:289-99. 1999..Ten out of 26 agouti mice are heterozygous ACHE knockout mice, and they are healthy and alive at 29 days of age. We expect a phenotype to appear in nullizygous animals... - Evidence for nonacetylcholinesterase targets of organophosphorus nerve agent: supersensitivity of acetylcholinesterase knockout mouse to VX lethalityE G Duysen
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
J Pharmacol Exp Ther 299:528-35. 2001..Organophosphorus ester toxicity in wild-type mice is probably due to inhibition or binding to several proteins, only one of which is AChE... - Prolonged toxic effects after cocaine challenge in butyrylcholinesterase/plasma carboxylesterase double knockout mice: a model for butyrylcholinesterase-deficient humansEllen G Duysen
University of Nebraska Medical Center, Eppley Institute, 985950 Nebraska Medical Center, Omaha, NE 68198 5950, USA
Drug Metab Dispos 39:1321-3. 2011.... - Engineering of a monomeric and low-glycosylated form of human butyrylcholinesterase: expression, purification, characterization and crystallizationFlorian Nachon
Centre de Recherches du Service de Sante des Armees, Unite d Enzymologie, La Tronche, France
Eur J Biochem 269:630-7. 2002..73 A3 per Da (estimated 60% solvent) for a single molecule of recombinant BChE in the asymmetric unit. The crystal structure of butyrylcholinesterase will help elucidate unsolved issues concerning cholinesterase mechanisms in general... - High activity of human butyrylcholinesterase at low pH in the presence of excess butyrylthiocholinePatrick Masson
Centre de Recherches du Service de Sante des Armees, Unite d Enzymologie, La Tronche, France
Eur J Biochem 270:315-24. 2003..The mechanism explaining the catalytic behaviour of butyrylcholinesterase at low pH in the presence of excess substrate remains to be elucidated... - Specificity of ethephon as a butyrylcholinesterase inhibitor and phosphorylating agentJ Eric Haux
Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA
Chem Res Toxicol 15:1527-33. 2002..More than a dozen other esterases examined are 10-100-fold less sensitive than BChE to ethephon. Thus, BChE inhibition continues to be the most sensitive marker of ethephon exposure... - Mutant of Bungarus fasciatus acetylcholinesterase with low affinity and low hydrolase activity toward organophosphorus estersThomas Poyot
Departement de Toxicologie, Centre de Recherches du Service de Sante des Armees, BP 87, 38702 La Tronche Cedex, France
Biochim Biophys Acta 1764:1470-8. 2006..DFP was characterised as a slow-binding substrate. This mutant is the first mutant of AChE capable of hydrolysing organophosphates. However, the overall OPase efficiency was greatly decreased compared to G117H butyrylcholinesterase... - A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein familyAntonella De Jaco
Department of Pharmacology, University of California San Diego, La Jolla, California 92093 0636, USA
J Biol Chem 281:9667-76. 2006..The mutation may alter the capacity of these proteins to dissociate from their chaperone prior to oligomerization and processing for export... - Re-engineering butyrylcholinesterase as a cocaine hydrolaseHong Sun
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation for Medical Education and Research, Rochester, Minnesota 55905, USA
Mol Pharmacol 62:220-4. 2002..This success demonstrates that computationally guided mutagenesis can generate functionally novel enzymes with clinical potential... - Substrate activation in acetylcholinesterase induced by low pH or mutation in the pi-cation subsitePatrick Masson
Centre de Recherches du Service de Sante des Armees, Unite d Enzymologie, La Tronche Cedex, France
Biochim Biophys Acta 1594:313-24. 2002..The finding that AChE is activated by excess substrate supports the idea that binding of a second substrate molecule to the PAS induces a conformational change that reorganizes the active site... - Altered hippocampal muscarinic receptors in acetylcholinesterase-deficient miceLaura A Volpicelli-Daley
Center for Neurodegenerative Disease and Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA
Ann Neurol 53:788-96. 2003..The alterations of mAChRs in AChE -/- mice suggest that mAChR downregulation may contribute to the limited efficacy of AChE inhibitors in Alzheimer's disease treatment... - Dramatic depletion of cell surface m2 muscarinic receptor due to limited delivery from intracytoplasmic stores in neurons of acetylcholinesterase-deficient miceVeronique Bernard
Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5541, Laboratoire d Histologie Embryologie, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, France
Mol Cell Neurosci 23:121-33. 2003.... - Neuropathological and immunochemical studies of brain parenchyma in acetylcholinesterase knockout mice: implications in Alzheimer's diseaseStephen G Rice
Barrow Neurological Institute, St Joseph s Hospital and Medical Center, Phoenix, AZ, USA
J Alzheimers Dis 11:481-9. 2007..Our studies show that neither the absence of AChE nor the presence exclusively of BChE is associated with neuroglial and vascular pathology... - Adaptation to excess acetylcholine by downregulation of adrenoceptors and muscarinic receptors in lungs of acetylcholinesterase knockout miceJaromir Myslivecek
Institute of Physiology, 1st Faculty of Medicine, Charles University, Albertov 5, 12800 Prague, Czech Republic
Naunyn Schmiedebergs Arch Pharmacol 376:83-92. 2007..Tolerance to excess acetylcholine is achieved by reducing the levels of muscarinic receptors and adrenoceptors... - Aryl acylamidase activity of human serum albumin with o-nitrotrifluoroacetanilide as the substratePatrick Masson
Centre de Recherches du Service de Sante des Armees, Unite d Enzymologie, BP 87, 38702 La Tronche Cedex, France
J Enzyme Inhib Med Chem 22:463-9. 2007..6-1 mM), albumin may participate in hydrolysis of aryl acylamides through second-order kinetics. This suggests that albumin may have a role in the metabolism of endogenous and exogenous aromatic amides, including drugs and xenobiotics... - Choline availability and acetylcholine synthesis in the hippocampus of acetylcholinesterase-deficient miceJoachim Hartmann
Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Science Center, Amarillo, TX, USA
Neurochem Int 52:972-8. 2008..Similar changes may take place in patients chronically exposed to AChE inhibitors... - Excessive hippocampal acetylcholine levels in acetylcholinesterase-deficient mice are moderated by butyrylcholinesterase activityJoachim Hartmann
Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Science Center, Amarillo, Texas 79106, USA
J Neurochem 100:1421-9. 2007..These results point to a potential usefulness of BChE inhibitors in the treatment of central cholinergic dysfunction in which brain AChE activity is typically reduced... - Naturally occurring mutation Leu307Pro of human butyrylcholinesterase in the Vysya community of IndiaIndumathi Manoharan
Bharathiar University, Department of Biotechnology, Coimbatore, Tamil Nadu, India
Pharmacogenet Genomics 16:461-8. 2006..People with genetic variants of butyrylcholinesterase (EC 3.1.1.8, BChE) can have hours of prolonged apnea after a normal dose of succinylcholine or mivacurium... - Reduced acetylcholine receptor density, morphological remodeling, and butyrylcholinesterase activity can sustain muscle function in acetylcholinesterase knockout miceMichael Adler
Neurotoxicology Branch, Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010, USA
Muscle Nerve 30:317-27. 2004..Studies of neuromuscular transmission in this model system provide an excellent opportunity to evaluate the role of AChE without complications arising from use of inhibitors... - Rate-determining step of butyrylcholinesterase-catalyzed hydrolysis of benzoylcholine and benzoylthiocholine. Volumetric study of wild-type and D70G mutant behaviorPatrick Masson
Centre de Recherches du Service de Santé des Armées CRSSA, Departement de Toxicologie, Unite d Enzymologie, 38702 La Tronche Cedex, France
Eur J Biochem 271:1980-90. 2004.... - Damped oscillatory hysteretic behaviour of butyrylcholinesterase with benzoylcholine as substratePatrick Masson
Centre de Recherches du Service de Sante des Armees, Departement de Toxicologie, Unite d Enzymologie, La Tronche, France
Eur J Biochem 271:220-34. 2004..1H-NMR measurements provided evidence for a slow equilibrium between two BzCh conformers. Binding of the conformationally preferred substrate conformer leads to products... - Altered striatal function and muscarinic cholinergic receptors in acetylcholinesterase knockout miceLaura A Volpicelli-Daley
Emory University School of Medicine, Whitehead Biomedical Research Building, 615 Michael St, 5th Floor, Atlanta, GA 30322, USA
Mol Pharmacol 64:1309-16. 2003..mAChR downregulation in AChE-/- mice has important implications for the long-term use of cholinesterase inhibitors and other cholinomimetics in treating disorders characterized by perturbed cholinergic function... - Aromatic amino-acid residues at the active and peripheral anionic sites control the binding of E2020 (Aricept) to cholinesterasesAshima Saxena
Division of Biochemistry, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Eur J Biochem 270:4447-58. 2003..The observation that the KI value for mutant AChE in which Ala replaced Trp286 is similar to that for wild-type BChE, further confirms our hypothesis... - Carbamates with differential mechanism of inhibition toward acetylcholinesterase and butyrylcholinesteraseSultan Darvesh
Department of Medicine Neurology, Dalhousie University, Halifax, Nova Scotia, Canada
J Med Chem 51:4200-12. 2008.... - Crystal structure of human butyrylcholinesterase and of its complexes with substrate and productsYvain Nicolet
Laboratoire de Cristallographie et Cristallogenese des Proteines, Institut de Biologie Structurale Jean Pierre Ebel, CEA, UJF, CNRS, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France
J Biol Chem 278:41141-7. 2003..An electron density peak close to the catalytic Ser(198) has been modeled as bound butyrate... - Impaired formation of the inner retina in an AChE knockout mouse results in degeneration of all photoreceptorsAfrim H Bytyqi
Darmstadt University of Technology, Developmental Biology and Neurogenetics, D 64287 Darmstadt, Germany
Eur J Neurosci 20:2953-62. 2004..These are the first in vivo findings to show a decisive role for AChE in the formation of the inner retinal network, which, when absent, ultimately results in photoreceptor degeneration... - A medical health report on individuals with silent butyrylcholinesterase in the Vysya community of IndiaIndumathi Manoharan
Bharathiar University, Department of Biotechnology, Coimbatore 641046, Tamil Nadu, India
Clin Chim Acta 378:128-35. 2007..A physiological function of BChE is to inactivate octanoyl ghrelin. We determined the health effect of complete absence of BChE in humans... - Intraperitoneal administration of 340 kDa human plasma butyrylcholinesterase increases the level of the enzyme in the cerebrospinal fluid of ratsJavier Saez-Valero
Instituto de Neurociencias de Alicante, Universidad Miguel Hernandez CSIC, E 03550 Sant Joan d Alacant, Spain
Neurosci Lett 383:93-8. 2005..BuChE in the CSF could serve to protect the brain from the neurotoxicity of organophosphorus pesticides and cocaine... - Five new naturally occurring mutations of the BCHE gene and frequencies of 12 butyrylcholinesterase alleles in a Brazilian populationLiya R Mikami
Department of Genetics, Federal University of Parana, Curitiba, Parana, Brazil
Pharmacogenet Genomics 18:213-8. 2008..Gene expression showed that only one of the newly identified mutations (G333C) altered BChE activity, leading to a decrease of about 80% in relation to the wild-type enzyme... - Cocaine metabolism accelerated by a re-engineered human butyrylcholinesteraseHong Sun
Molecular Neuroscience Program, Mayo Foundation for Medical Education and Research, 200 First Street Southwest, Rochester, MN 55905, USA
J Pharmacol Exp Ther 302:710-6. 2002..These results show that A328W/Y332A, an efficient cocaine hydrolase in vivo as well as in vitro, might promote cocaine detoxication in a clinical setting...
Research Grants
- Mass Spectrometry in Clinical Diagnosis of Nerve Agent ExposureOksana Lockridge; Fiscal Year: 2007..The new diagnostic methods have the potential for saving lives in an emergency because correct, rapid diagnosis indicates the appropriate medical treatment. ..