Readthrough acetylcholinesterase in inflammation-associated neuropathies

Amir Dori, Gal Ifergane, Tal Saar-Levy, Marina Bersudsky, Inbal Mor, Hermona Soreq, Itzhak Wirguin

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The cholinergic control over inflammatory reactions calls for deciphering the corresponding protein partners. An example is blood-nerve barrier disruption allowing penetration of inflammatory factors, which is notably involved in various neuropathies due to yet unknown molecular mechanism(s). In rats, lipopolysaccharide (LPS) administration followed by intra-neural (i.n.) saline injection inducing a focal blood-nerve disruption leads to systemic inflammatory reaction accompanied by transient conduction impairment in the sciatic nerve. Here, we provide evidence compatible with the hypothesis that ARP, the naturally cleavable C-terminal peptide of the stress-induced "readthrough" acetylcholinesterase variant (AChE-R), is causally involved in the emergence of this LPS-induced conduction impairment. Intra-neural injection to naïve rats of conditioned medium from cultured splenocytes exposed to LPS in vitro (reactive splenocyte medium) induced a transient conduction impairment that was accompanied by facilitated accumulation of cleaved intra-neural ARP. Protein kinase C (PKC) βII, known to interact with ARP, was significantly elevated in the LPS-exposed sciatic nerve preparations. Moreover, direct i.n. injection of synthetic ARP30, bearing the mouse AChE-R C-terminal sequence, similarly induced PKCβII expression and conduction impairment. The induction of neural conduction impairment by ARP, possibly through its interaction with PKCβII, suggests a role for AChE-R expression in inflammation-associated neuropathies.

Original languageEnglish
Pages (from-to)2369-2374
Number of pages6
JournalLife Sciences
Volume80
Issue number24-25
DOIs
StatePublished - 30 May 2007
Externally publishedYes

Keywords

  • Acetylcholinesterase
  • Inflammation neuropathy
  • Readthrough acetylcholinesterase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Pharmacology, Toxicology and Pharmaceutics (all)

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