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

22 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Toxicology

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