Differential sensitivity of plasma carboxylesterase-null mice to parathion, chlorpyrifos and chlorpyrifos oxon, but not to diazinon, dichlorvos, diisopropylfluorophosphate, cresyl saligenin phosphate, cyclosarin thiocholine, tabun thiocholine, and carbofuEllen G Duysen
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 5950, USA
Chem Biol Interact 195:189-98. 2012
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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...
- 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...
- 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...
- 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...
- 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...
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...
- 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...
- 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...
- 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...
- Production of ES1 plasma carboxylesterase knockout mice for toxicity studies
Ellen G Duysen
Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198 5950, USA
Chem Res Toxicol 24:1891-8. 2011
..The ES1-/- mouse should be an appropriate model for testing highly toxic nerve agents and for evaluating protection strategies against the toxicity of nerve agents...
- 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...
- 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...
- 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...
- Mice treated with a nontoxic dose of chlorpyrifos oxon have diethoxyphosphotyrosine labeled proteins in blood up to 4 days post exposure, detected by mass spectrometry
Wei Jiang
Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, Omaha, NE 68198 5950, United States
Toxicology 295:15-22. 2012
..In contrast plasma AChE activity returned to normal after 24-72 h. In conclusion MALDI-TOF mass spectrometry can be used to diagnose exposure to chlorpyrifos oxon days after AChE inhibition assays are uninformative...
- 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...
- Induction of plasma acetylcholinesterase activity in mice challenged with organophosphorus poisons
Ellen G Duysen
Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 5950, USA
Toxicol Appl Pharmacol 255:214-20. 2011
..We hypothesize that acetylcholinesterase activity is induced when cells undergo apoptosis and that consequently there is a rise in the level of plasma acetylcholinesterase...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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
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- 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...
- 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...
- 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...
