title: Adaptive changes in acetylcholinesterase gene expression as mediators of recovery from chemical and biological insults.
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.
authors.affiliation: Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Tama
authors.initials: T
authors.lastname: Evron
authors.forename: David
authors.initials: D
authors.lastname: Greenberg
authors.forename: Tsafrir S
authors.initials: TS
authors.lastname: Mor
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D016466:CHO Cells; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood / Q000235:genetics*; D003345:Corticosterone / Q000097:blood; D006224:Cricetinae; D003412:Cricetulus; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D010261:Paraoxon / Q000633:toxicity*; D010446:Peptide Fragments / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D002802:Cholinesterases; D010261:Paraoxon; D003345:Corticosterone