Hagstrom_2017_Arch.Toxicol_91_2837

Reference

Title : Planarian cholinesterase: in vitro characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity and reactivation - Hagstrom_2017_Arch.Toxicol_91_2837
Author(s) : Hagstrom D , Hirokawa H , Zhang L , Radic Z , Taylor P , Collins ES
Ref : Archives of Toxicology , 91 :2837 , 2016
Abstract :

The freshwater planarian Dugesia japonica has recently emerged as an animal model for developmental neurotoxicology and found to be sensitive to organophosphorus (OP) pesticides. While previous activity staining of D. japonica, which possess a discrete cholinergic nervous system, has shown acylthiocholine catalysis, it is unknown whether this is accomplished through an acetylcholinesterase (AChE), butyrylcholinesterase (BChE), or a hybrid esterase and how OP exposure affects esterase activity. Here, we show that the majority of D. japonica cholinesterase (DjChE) activity departs from conventional AChE and BChE classifications. Inhibition by classic protonable amine and quaternary reversible inhibitors (ethopropazine, donepezil, tacrine, edrophonium, BW284c51, propidium) shows that DjChE is far less sensitive to these inhibitors than human AChE, suggesting discrete differences in active center and peripheral site recognition and structures. Additionally, we find that different OPs (chlorpyrifos oxon, paraoxon, dichlorvos, diazinon oxon, malaoxon) and carbamylating agents (carbaryl, neostigmine, physostigmine, pyridostigmine) differentially inhibit DjChE activity in vitro. DjChE was most sensitive to diazinon oxon and neostigmine and least sensitive to malaoxon and carbaryl. Diazinon oxon-inhibited DjChE could be reactivated by the quaternary oxime, pralidoxime (2-PAM), and the zwitterionic oxime, RS194B, with RS194B being significantly more potent. Sodium fluoride (NaF) reactivates OP-DjChE faster than 2-PAM. As one of the most ancient true cholinesterases, DjChE provides insight into the evolution of a hybrid enzyme before the separation into distinct AChE and BChE enzymes found in higher vertebrates. The sensitivity of DjChE to OPs and capacity for reactivation validate the use of planarians for OP toxicology studies.

PubMedSearch : Hagstrom_2017_Arch.Toxicol_91_2837
PubMedID: 27990564
Gene_locus related to this paper: dugja-CHE1 , dugja-CHE2

Related information

Gene_locus dugja-CHE1    dugja-CHE2
Reactivator dugja-CHE1    dugja-CHE2    RS194B

Citations formats

Hagstrom D, Hirokawa H, Zhang L, Radic Z, Taylor P, Collins ES (2016)
Planarian cholinesterase: in vitro characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity and reactivation
Archives of Toxicology 91 :2837

Hagstrom D, Hirokawa H, Zhang L, Radic Z, Taylor P, Collins ES (2016)
Archives of Toxicology 91 :2837