Adaptive changes in acetylcholinesterase gene expression as mediators of recovery from chemical and biological insults

Tama Evron, David Greenberg, Tsafrir Leket-Mor, Hermona Soreq

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Both organophosphate (OP) exposure and bacterial infection notably induce short- and long-term cholinergic responses. These span the central and peripheral nervous system, neuromuscular pathway and hematopoietic cells and involve over-expression of the "readthrough" variant of acetylcholinesterase, AChE-R, and its naturally cleavable C-terminal peptide ARP. However, the causal involvement of these changes with post-exposure recovery as opposed to apoptotic events remained to be demonstrated. Here, we report the establishment of stably transfected cell lines expressing catalytically active human "synaptic" AChE-S or AChE-R which are fully viable and non-apoptotic. In addition, intraperitoneally injected synthetic mouse ARP (mARP) elevated serum AChE levels post-paraoxon exposure. Moreover, mARP treatment ameliorated post-exposure increases in corticosterone and decreases in AChE gene expression and facilitated earlier retrieval of motor activity following both paraoxon and lipopolysaccharide (LPS) exposures. Our findings suggest a potential physiological role for overproduction of AChE-R and the ARP peptide following exposure to both chemical warfare agents and bacterial LPS.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
JournalToxicology
Volume233
Issue number1-3 SPEC. ISS.
DOIs
StatePublished - Apr 20 2007

Fingerprint

Paraoxon
Acetylcholinesterase
Gene expression
Lipopolysaccharides
Chemical Warfare Agents
Gene Expression
Recovery
Peptides
Organophosphates
Peripheral Nervous System
Neurology
Corticosterone
Bacterial Infections
Cholinergic Agents
Motor Activity
Central Nervous System
Cells
Cell Line
Serum
R peptide

Keywords

  • Acetylcholinesterase
  • Body temperature
  • Gene expression
  • Motor activity
  • Paraoxon

ASJC Scopus subject areas

  • Toxicology

Cite this

Adaptive changes in acetylcholinesterase gene expression as mediators of recovery from chemical and biological insults. / Evron, Tama; Greenberg, David; Leket-Mor, Tsafrir; Soreq, Hermona.

In: Toxicology, Vol. 233, No. 1-3 SPEC. ISS., 20.04.2007, p. 97-107.

Research output: Contribution to journalArticle

Evron, Tama ; Greenberg, David ; Leket-Mor, Tsafrir ; Soreq, Hermona. / Adaptive changes in acetylcholinesterase gene expression as mediators of recovery from chemical and biological insults. In: Toxicology. 2007 ; Vol. 233, No. 1-3 SPEC. ISS. pp. 97-107.
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