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.
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Authors | Tanvisith Charoenying, Tawit Suriyo, Apinya Thiantanawat, Sansanee C Chaiyaroj, Preeda Parkpian, Jutamaad Satayavivad |
Journal | Environmental toxicology and pharmacology
(Environ Toxicol Pharmacol)
Vol. 31
Issue 1
Pg. 119-28
(Jan 2011)
ISSN: 1872-7077 [Electronic] Netherlands |
PMID | 21787676
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010. Published by Elsevier B.V. |
Chemical References |
- Cholinesterase Inhibitors
- Coloring Agents
- Indicators and Reagents
- Muscarinic Agonists
- Receptor, Muscarinic M1
- Receptor, Muscarinic M2
- Receptor, Muscarinic M3
- Tetrazolium Salts
- Thiazoles
- Acetylcholinesterase
- thiazolyl blue
- Paraoxon
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Topics |
- Acetylcholinesterase
(metabolism)
- Blotting, Western
- Cell Line
- Cell Survival
(drug effects)
- Cholinesterase Inhibitors
(toxicity)
- Coloring Agents
- Genes, fos
(drug effects)
- Humans
- Indicators and Reagents
- Lymphocytes
(drug effects)
- Muscarinic Agonists
(toxicity)
- Neurons
(drug effects)
- Paraoxon
(toxicity)
- Parasympathetic Nervous System
(cytology, drug effects)
- Real-Time Polymerase Chain Reaction
- Receptor, Muscarinic M1
(drug effects)
- Receptor, Muscarinic M2
(drug effects)
- Receptor, Muscarinic M3
(drug effects)
- Tetrazolium Salts
- Thiazoles
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