O Lockridge

Summary

Affiliation: University of Nebraska Medical Center
Country: USA

Publications

  1. ncbi request reprint DNA sequence of butyrylcholinesterase from the rat: expression of the protein and characterization of the properties of rat butyrylcholinesterase
    Andreea Ticu Boeck
    Eppley Institute, 986805, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
    Biochem Pharmacol 63:2101-10. 2002
  2. ncbi request reprint Rescue of the acetylcholinesterase knockout mouse by feeding a liquid diet; phenotype of the adult acetylcholinesterase deficient mouse
    Ellen G Duysen
    Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 6805, USA
    Brain Res Dev Brain Res 137:43-54. 2002
  3. pmc Five tyrosines and two serines in human albumin are labeled by the organophosphorus agent FP-biotin
    Shi Jian Ding
    Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
    Chem Res Toxicol 21:1787-94. 2008
  4. pmc Review of tyrosine and lysine as new motifs for organophosphate binding to proteins that have no active site serine
    Oksana Lockridge
    Eppley Institute, 985950 University of Nebraska Medical Center, Omaha, NE 68198 5950, United States
    Chem Biol Interact 187:344-8. 2010
  5. ncbi request reprint Pesticides and susceptible populations: people with butyrylcholinesterase genetic variants may be at risk
    O Lockridge
    University of Nebraska Medical Center, Eppley Institute, Omaha 68198 6805, USA
    Neurotoxicology 21:113-26. 2000
  6. ncbi request reprint A single amino acid substitution, Gly117His, confers phosphotriesterase (organophosphorus acid anhydride hydrolase) activity on human butyrylcholinesterase
    O Lockridge
    Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
    Biochemistry 36:786-95. 1997
  7. ncbi request reprint Tryptophan residue(s) as major components of the human serum paraoxonase active site
    D Josse
    Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
    Chem Biol Interact 119:79-84. 1999
  8. pmc Importance of aspartate-70 in organophosphate inhibition, oxime re-activation and aging of human butyrylcholinesterase
    P 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
  9. ncbi request reprint Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouse
    B Li
    Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
    J Neurochem 75:1320-31. 2000
  10. ncbi request reprint Evidence for nonacetylcholinesterase targets of organophosphorus nerve agent: supersensitivity of acetylcholinesterase knockout mouse to VX lethality
    E G Duysen
    Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 6805, USA
    J Pharmacol Exp Ther 299:528-35. 2001

Research Grants

Collaborators

Detail Information

Publications97

  1. ncbi request reprint DNA sequence of butyrylcholinesterase from the rat: expression of the protein and characterization of the properties of rat butyrylcholinesterase
    Andreea 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...
  2. ncbi request reprint Rescue of the acetylcholinesterase knockout mouse by feeding a liquid diet; phenotype of the adult acetylcholinesterase deficient mouse
    Ellen 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...
  3. pmc Five tyrosines and two serines in human albumin are labeled by the organophosphorus agent FP-biotin
    Shi 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...
  4. pmc Review of tyrosine and lysine as new motifs for organophosphate binding to proteins that have no active site serine
    Oksana 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...
  5. ncbi request reprint Pesticides and susceptible populations: people with butyrylcholinesterase genetic variants may be at risk
    O 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...
  6. ncbi request reprint A single amino acid substitution, Gly117His, confers phosphotriesterase (organophosphorus acid anhydride hydrolase) activity on human butyrylcholinesterase
    O 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...
  7. ncbi request reprint Tryptophan residue(s) as major components of the human serum paraoxonase active site
    D 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...
  8. pmc Importance of aspartate-70 in organophosphate inhibition, oxime re-activation and aging of human butyrylcholinesterase
    P 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...
  9. ncbi request reprint Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouse
    B 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...
  10. ncbi request reprint Evidence for nonacetylcholinesterase targets of organophosphorus nerve agent: supersensitivity of acetylcholinesterase knockout mouse to VX lethality
    E 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...
  11. ncbi request reprint 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...
  12. ncbi request reprint Human serum paraoxonase (PON1): identification of essential amino acid residues by group-selective labelling and site-directed mutagenesis
    D 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...
  13. ncbi request reprint Albumin, a new biomarker of organophosphorus toxicant exposure, identified by mass spectrometry
    Eric 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...
  14. ncbi request reprint Butyrylcholinesterase, paraoxonase, and albumin esterase, but not carboxylesterase, are present in human plasma
    Bin 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...
  15. pmc Mass spectrometry identifies multiple organophosphorylated sites on tubulin
    Hasmik 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...
  16. pmc Pseudo-esterase activity of human albumin: slow turnover on tyrosine 411 and stable acetylation of 82 residues including 59 lysines
    Oksana 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...
  17. ncbi request reprint Role of water in aging of human butyrylcholinesterase inhibited by echothiophate: the crystal structure suggests two alternative mechanisms of aging
    Florian 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...
  18. ncbi request reprint Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesterase
    Liya 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...
  19. ncbi request reprint 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 toxicity
    Ellen 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...
  20. pmc 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 agents
    Wei 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...
  21. pmc Mass spectral characterization of organophosphate-labeled lysine in peptides
    Hasmik 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...
  22. pmc Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay for organophosphorus toxicants bound to human albumin at Tyr411
    Bin 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...
  23. pmc 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 agents
    Hasmik 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...
  24. doi request reprint Adenovirus-mediated human paraoxonase1 gene transfer to provide protection against the toxicity of the organophosphorus pesticide toxicant diazoxon
    E 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...
  25. ncbi request reprint Kinetic analysis of effector modulation of butyrylcholinesterase-catalysed hydrolysis of acetanilides and homologous esters
    Patrick 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...
  26. ncbi request reprint Phenotype comparison of three acetylcholinesterase knockout strains
    Ellen 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...
  27. ncbi request reprint Hysteresis of butyrylcholinesterase in the approach to steady-state kinetics
    Patrick 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...
  28. ncbi request reprint Hydrolysis of oxo- and thio-esters by human butyrylcholinesterase
    Patrick 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...
  29. ncbi request reprint Markers of organophosphate exposure in human serum
    Stacy 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...
  30. ncbi request reprint The butyrylcholinesterase knockout mouse is obese on a high-fat diet
    Bin 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...
  31. ncbi request reprint Whole body and tissue imaging of the butyrylcholinesterase knockout mouse injected with near infrared dye labeled butyrylcholinesterase
    Ellen 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...
  32. ncbi request reprint 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...
  33. ncbi request reprint 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 neurotransmission
    Ellen 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...
  34. ncbi request reprint Reaction kinetics of biotinylated organophosphorus toxicant, FP-biotin, with human acetylcholinesterase and human butyrylcholinesterase
    Lawrence 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...
  35. ncbi request reprint Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometry
    He 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...
  36. ncbi request reprint Structural approach to the aging of phosphylated cholinesterases
    Patrick 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...
  37. pmc Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behavior
    Patrick 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...
  38. pmc Mass spectral characterization of organophosphate-labeled, tyrosine-containing peptides: characteristic mass fragments and a new binding motif for organophosphates
    Lawrence 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...
  39. pmc Nanoimages show disruption of tubulin polymerization by chlorpyrifos oxon: implications for neurotoxicity
    Hasmik 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...
  40. pmc Covalent binding of the organophosphorus agent FP-biotin to tyrosine in eight proteins that have no active site serine
    Hasmik 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...
  41. ncbi request reprint The butyrylcholinesterase knockout mouse a research tool in the study of drug sensitivity, bio-distribution, obesity and Alzheimer's disease
    Ellen 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...
  42. doi request reprint Carbofuran poisoning detected by mass spectrometry of butyrylcholinesterase adduct in human serum
    He 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...
  43. pmc Development of diagnostics in the search for an explanation of aerotoxic syndrome
    Lawrence 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...
  44. ncbi request reprint A collaborative endeavor to design cholinesterase-based catalytic scavengers against toxic organophosphorus esters
    Patrick 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...
  45. ncbi request reprint Determination of the DNA sequences of acetylcholinesterase and butyrylcholinesterase from cat and demonstration of the existence of both in cat plasma
    C 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...
  46. ncbi request reprint Conserved aromatic residues of the C-terminus of human butyrylcholinesterase mediate the association of tetramers
    C V Altamirano
    Department of Biochemistry and Molecular Biology, Eppley Institute, University of Nebraska Medical Center, Omaha 68198 6805, USA
    Biochemistry 38:13414-22. 1999
    ....
  47. ncbi request reprint Gene transfer of acetylcholinesterase protects the knockout mouse from the toxicity of DFP
    Bin 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...
  48. ncbi request reprint Regulation of muscarinic acetylcholine receptor function in acetylcholinesterase knockout mice
    Bin 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...
  49. ncbi request reprint Lamellipodin proline rich peptides associated with native plasma butyrylcholinesterase tetramers
    He 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...
  50. doi request reprint Binding and hydrolysis of soman by human serum albumin
    Bin 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...
  51. ncbi request reprint Naturally occurring mutation, Asp70his, in human butyrylcholinesterase
    Andreea Ticu Boeck
    University of Nebraska Medical Center, Eppley Institute, Omaha, Nebraska 68198 6805, USA
    Ann Clin Biochem 39:154-6. 2002
    ..People with genetic variants of butyrylcholinesterase can have hours of prolonged apnoea after a normal dose of succinylcholine or mivacurium...
  52. pmc Tyrosines of human and mouse transferrin covalently labeled by organophosphorus agents: a new motif for binding to proteins that have no active site serine
    Bin 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...
  53. ncbi request reprint Resistance to organophosphorus agent toxicity in transgenic mice expressing the G117H mutant of human butyrylcholinesterase
    Yuxia 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...
  54. ncbi request reprint Screening assays for cholinesterases resistant to inhibition by organophosphorus toxicants
    Yuxia 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...
  55. pmc Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene accounts for YT blood group polymorphism
    C 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...
  56. ncbi request reprint Protection from the toxicity of diisopropylfluorophosphate by adeno-associated virus expressing acetylcholinesterase
    Bin 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...
  57. ncbi request reprint Delivery of human acetylcholinesterase by adeno-associated virus to the acetylcholinesterase knockout mouse
    Anna 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...
  58. ncbi request reprint Identification of organophosphate-reactive proteins by tandem mass spectrometry
    He Li
    Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 18105, USA
    Chem Biol Interact 157:383-4. 2005
  59. pmc Intrathecal delivery of fluorescent labeled butyrylcholinesterase to the brains of butyrylcholinesterase knock-out mice: visualization and quantification of enzyme distribution in the brain
    Noel 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...
  60. ncbi request reprint The butyrylcholinesterase knockout mouse as a model for human butyrylcholinesterase deficiency
    Bin 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...
  61. ncbi request reprint Fast affinity purification coupled with mass spectrometry for identifying organophosphate labeled plasma butyrylcholinesterase
    He 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...
  62. pmc Crystallization and X-ray structure of full-length recombinant human butyrylcholinesterase
    Michelle 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...
  63. ncbi request reprint Increased hepatotoxicity and cardiac fibrosis in cocaine-treated butyrylcholinesterase knockout mice
    Ellen 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...
  64. ncbi request reprint Production of the butyrylcholinesterase knockout mouse
    Bin 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...
  65. ncbi request reprint Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase
    W 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...
  66. pmc Reaction of human albumin with aspirin in vitro: mass spectrometric identification of acetylated lysines 199, 402, 519, and 545
    Mariya 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...
  67. pmc Detection of adduct on tyrosine 411 of albumin in humans poisoned by dichlorvos
    Bin 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...
  68. ncbi request reprint Early weaning and culling eradicated Helicobacter hepaticus from an acetylcholinesterase knockout 129S6/SvEvTac mouse colony
    Ellen 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...
  69. ncbi request reprint Knockout of one acetylcholinesterase allele in the mouse
    W 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...
  70. doi request reprint Prolonged toxic effects after cocaine challenge in butyrylcholinesterase/plasma carboxylesterase double knockout mice: a model for butyrylcholinesterase-deficient humans
    Ellen 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
    ....
  71. ncbi request reprint Altered hippocampal muscarinic receptors in acetylcholinesterase-deficient mice
    Laura 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...
  72. ncbi request reprint Dramatic depletion of cell surface m2 muscarinic receptor due to limited delivery from intracytoplasmic stores in neurons of acetylcholinesterase-deficient mice
    Veronique 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
    ....
  73. ncbi request reprint Mutant of Bungarus fasciatus acetylcholinesterase with low affinity and low hydrolase activity toward organophosphorus esters
    Thomas 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...
  74. ncbi request reprint Engineering of a monomeric and low-glycosylated form of human butyrylcholinesterase: expression, purification, characterization and crystallization
    Florian 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...
  75. ncbi request reprint Specificity of ethephon as a butyrylcholinesterase inhibitor and phosphorylating agent
    J 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...
  76. ncbi request reprint High activity of human butyrylcholinesterase at low pH in the presence of excess butyrylthiocholine
    Patrick 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...
  77. ncbi request reprint Re-engineering butyrylcholinesterase as a cocaine hydrolase
    Hong 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...
  78. ncbi request reprint Substrate activation in acetylcholinesterase induced by low pH or mutation in the pi-cation subsite
    Patrick 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...
  79. ncbi request reprint Damped oscillatory hysteretic behaviour of butyrylcholinesterase with benzoylcholine as substrate
    Patrick 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...
  80. ncbi request reprint Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products
    Yvain 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...
  81. ncbi request reprint Aromatic amino-acid residues at the active and peripheral anionic sites control the binding of E2020 (Aricept) to cholinesterases
    Ashima 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...
  82. ncbi request reprint Excessive hippocampal acetylcholine levels in acetylcholinesterase-deficient mice are moderated by butyrylcholinesterase activity
    Joachim 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...
  83. ncbi request reprint Neuropathological and immunochemical studies of brain parenchyma in acetylcholinesterase knockout mice: implications in Alzheimer's disease
    Stephen 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...
  84. ncbi request reprint Impaired formation of the inner retina in an AChE knockout mouse results in degeneration of all photoreceptors
    Afrim 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...
  85. ncbi request reprint Adaptation to excess acetylcholine by downregulation of adrenoceptors and muscarinic receptors in lungs of acetylcholinesterase knockout mice
    Jaromir 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...
  86. ncbi request reprint Aryl acylamidase activity of human serum albumin with o-nitrotrifluoroacetanilide as the substrate
    Patrick 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...
  87. ncbi request reprint A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family
    Antonella 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...
  88. ncbi request reprint Choline availability and acetylcholine synthesis in the hippocampus of acetylcholinesterase-deficient mice
    Joachim 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...
  89. ncbi request reprint Altered striatal function and muscarinic cholinergic receptors in acetylcholinesterase knockout mice
    Laura 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...
  90. ncbi request reprint Naturally occurring mutation Leu307Pro of human butyrylcholinesterase in the Vysya community of India
    Indumathi 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...
  91. doi request reprint Carbamates with differential mechanism of inhibition toward acetylcholinesterase and butyrylcholinesterase
    Sultan Darvesh
    Department of Medicine Neurology, Dalhousie University, Halifax, Nova Scotia, Canada
    J Med Chem 51:4200-12. 2008
    ....
  92. ncbi request reprint Rate-determining step of butyrylcholinesterase-catalyzed hydrolysis of benzoylcholine and benzoylthiocholine. Volumetric study of wild-type and D70G mutant behavior
    Patrick 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
    ....
  93. ncbi request reprint Reduced acetylcholine receptor density, morphological remodeling, and butyrylcholinesterase activity can sustain muscle function in acetylcholinesterase knockout mice
    Michael 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...
  94. ncbi request reprint Cocaine metabolism accelerated by a re-engineered human butyrylcholinesterase
    Hong 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...
  95. ncbi request reprint A medical health report on individuals with silent butyrylcholinesterase in the Vysya community of India
    Indumathi 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...
  96. ncbi request reprint Intraperitoneal administration of 340 kDa human plasma butyrylcholinesterase increases the level of the enzyme in the cerebrospinal fluid of rats
    Javier 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...
  97. ncbi request reprint Five new naturally occurring mutations of the BCHE gene and frequencies of 12 butyrylcholinesterase alleles in a Brazilian population
    Liya 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...

Research Grants2

  1. Mass Spectrometry in Clinical Diagnosis of Nerve Agent Exposure
    Oksana 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. ..