Noncholinesterase Protein Targets of Organophosphorus Pesticides

Oksana Lockridge

doi:10.1016/B978-0-444-62645-5.00005-5

Noncholinesterase Protein Targets of Organophosphorus Pesticides

Oksana Lockridge

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

The acute toxicity of organophosphorus (OP) nerve agents and pesticides is due to inhibition of acetylcholinesterase (AChE) activity in cholinergic nerve synapses. Delayed neuropathy involves OP binding to neuropathy target esterase (NTE) in neurons. AChE and NTE are serine hydrolases. In vitro studies have demonstrated that OP toxicants bind not only to serine hydrolases but also to proteins that have no active site serine, for example, Tyr 411 of human albumin and Lys 296 of mouse transferrin. Mice treated with low doses of chlorpyrifos have OP-modified tubulin in brain. Mass spectrometry has identified OP-modified albumin in the blood of humans self-poisoned by chlorpyrifos and dichlorvos. Albumin is weakly reactive with OP, but the presence of OP-modified albumin in humans suggests the existence of additional noncholinesterase OP targets. In conclusion, long-term adverse effects from OP exposure may involve OP modification of proteins that have no active site serine.

Original language	English (US)
Pages (from-to)	179-205
Number of pages	27
Journal	Advances in Molecular Toxicology
Volume	7
DOIs	https://doi.org/10.1016/B978-0-444-62645-5.00005-5
State	Published - 2013

Keywords

Acylpeptide hydrolase
Albumin
Mass spectrometry
Neuropathy target esterase
Organophosphorus toxicants
Tubulin

ASJC Scopus subject areas

Health, Toxicology and Mutagenesis
Pharmacology
Toxicology

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10.1016/B978-0-444-62645-5.00005-5

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@article{564f645861174b59b74eb22097baf915,

title = "Noncholinesterase Protein Targets of Organophosphorus Pesticides",

abstract = "The acute toxicity of organophosphorus (OP) nerve agents and pesticides is due to inhibition of acetylcholinesterase (AChE) activity in cholinergic nerve synapses. Delayed neuropathy involves OP binding to neuropathy target esterase (NTE) in neurons. AChE and NTE are serine hydrolases. In vitro studies have demonstrated that OP toxicants bind not only to serine hydrolases but also to proteins that have no active site serine, for example, Tyr 411 of human albumin and Lys 296 of mouse transferrin. Mice treated with low doses of chlorpyrifos have OP-modified tubulin in brain. Mass spectrometry has identified OP-modified albumin in the blood of humans self-poisoned by chlorpyrifos and dichlorvos. Albumin is weakly reactive with OP, but the presence of OP-modified albumin in humans suggests the existence of additional noncholinesterase OP targets. In conclusion, long-term adverse effects from OP exposure may involve OP modification of proteins that have no active site serine.",

keywords = "Acylpeptide hydrolase, Albumin, Mass spectrometry, Neuropathy target esterase, Organophosphorus toxicants, Tubulin",

author = "Oksana Lockridge",

year = "2013",

doi = "10.1016/B978-0-444-62645-5.00005-5",

language = "English (US)",

volume = "7",

pages = "179--205",

journal = "Advances in Molecular Toxicology",

issn = "1872-0854",

publisher = "Elsevier",

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T1 - Noncholinesterase Protein Targets of Organophosphorus Pesticides

AU - Lockridge, Oksana

PY - 2013

Y1 - 2013

N2 - The acute toxicity of organophosphorus (OP) nerve agents and pesticides is due to inhibition of acetylcholinesterase (AChE) activity in cholinergic nerve synapses. Delayed neuropathy involves OP binding to neuropathy target esterase (NTE) in neurons. AChE and NTE are serine hydrolases. In vitro studies have demonstrated that OP toxicants bind not only to serine hydrolases but also to proteins that have no active site serine, for example, Tyr 411 of human albumin and Lys 296 of mouse transferrin. Mice treated with low doses of chlorpyrifos have OP-modified tubulin in brain. Mass spectrometry has identified OP-modified albumin in the blood of humans self-poisoned by chlorpyrifos and dichlorvos. Albumin is weakly reactive with OP, but the presence of OP-modified albumin in humans suggests the existence of additional noncholinesterase OP targets. In conclusion, long-term adverse effects from OP exposure may involve OP modification of proteins that have no active site serine.

AB - The acute toxicity of organophosphorus (OP) nerve agents and pesticides is due to inhibition of acetylcholinesterase (AChE) activity in cholinergic nerve synapses. Delayed neuropathy involves OP binding to neuropathy target esterase (NTE) in neurons. AChE and NTE are serine hydrolases. In vitro studies have demonstrated that OP toxicants bind not only to serine hydrolases but also to proteins that have no active site serine, for example, Tyr 411 of human albumin and Lys 296 of mouse transferrin. Mice treated with low doses of chlorpyrifos have OP-modified tubulin in brain. Mass spectrometry has identified OP-modified albumin in the blood of humans self-poisoned by chlorpyrifos and dichlorvos. Albumin is weakly reactive with OP, but the presence of OP-modified albumin in humans suggests the existence of additional noncholinesterase OP targets. In conclusion, long-term adverse effects from OP exposure may involve OP modification of proteins that have no active site serine.

KW - Acylpeptide hydrolase

KW - Albumin

KW - Mass spectrometry

KW - Neuropathy target esterase

KW - Organophosphorus toxicants

KW - Tubulin

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U2 - 10.1016/B978-0-444-62645-5.00005-5

DO - 10.1016/B978-0-444-62645-5.00005-5

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SN - 1872-0854

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EP - 205

JO - Advances in Molecular Toxicology

JF - Advances in Molecular Toxicology

ER -

Noncholinesterase Protein Targets of Organophosphorus Pesticides

Abstract

Keywords

ASJC Scopus subject areas

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