Effects of paraoxon on neuronal and lymphocytic cholinergic systems

Abstract The cholinergic system in lymphocytes is hypothesized to be a key target for neurotoxic organophosphates (OPs). The present study determined the comparative effects of paraoxon, the active metabolite of OP-parathion, which is detected in the human neuroblastoma line, SH-SY5Y, and leukemic T...

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Published in:Environmental toxicology and pharmacology 2011-01, Vol.31 (1), p.119-128
Main Authors: Charoenying, Tanvisith, Suriyo, Tawit, Thiantanawat, Apinya, Chaiyaroj, Sansanee C, Parkpian, Preeda, Satayavivad, Jutamaad
Format: Article
Language:English
Subjects:
Acetylcholinesterase - metabolism
Blotting, Western
c-Fos
Cell Line
Cell Survival - drug effects
Cholinesterase Inhibitors - toxicity
Coloring Agents
Emergency
Genes, fos - drug effects
Humans
Indicators and Reagents
Lymphocytes - drug effects
MOLT-3
Muscarinic acetylcholine receptors
Muscarinic Agonists - toxicity
Neurons - drug effects
Non-neuronal lymphocytic cholinergic system
Paraoxon
Paraoxon - toxicity
Parasympathetic Nervous System - cytology
Parasympathetic Nervous System - drug effects
Real-Time Polymerase Chain Reaction
Receptor, Muscarinic M1 - drug effects
Receptor, Muscarinic M2 - drug effects
Receptor, Muscarinic M3 - drug effects
SH-SY5Y
Tetrazolium Salts
Thiazoles
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Summary:Abstract The cholinergic system in lymphocytes is hypothesized to be a key target for neurotoxic organophosphates (OPs). The present study determined the comparative effects of paraoxon, the active metabolite of OP-parathion, which is detected in the human neuroblastoma line, SH-SY5Y, and leukemic T-lymphocytes, MOLT-3, in vitro . Paraoxon induced cytotoxic effects in a dose- and time-dependent manner in both cells. Further, the paraoxon-induced modulatory effects were comparable despite different cell types, including over-expression of N-terminus acetylcholinesterase (N-AChE) protein, a marker of apoptosis, down-regulations of mRNA encoding M1, M2, and M3 muscarinic acetylcholine receptors (mAChRs), and induction in expression of c-Fos gene, an indication of certain mAChR subtype(s) activation. Furthermore, the non-selective cholinergic antagonist atropine partially attenuated the paraoxon-induced N-AChE and c-Fos activations in both types of cells. These results provide initial and additional information that OPs may similarly induce neuro- and immuno-toxic effects through mAChRs activation, and they underline the potential of using lymphocytes for assessing OPs-induced neurotoxicity.
ISSN:1382-6689
1872-7077
DOI:10.1016/j.etap.2010.09.012