ToxSci Advance Access originally published online on April 6, 2009
Toxicological Sciences 2009 109(2):276-285; doi:10.1093/toxsci/kfp068
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The Homeostasis of Phosphatidylcholine and Lysophosphatidylcholine in Nervous Tissues of Mice was not Disrupted after Administration of Tri-o-cresyl Phosphate
* Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China
Graduate School of the Chinese Academy of Sciences, Beijing 100039, P.R. China
1 To whom correspondence should be addressed at Institute of Zoology, CAS, Datunlu Road, Beijing 100101, P.R. China. Fax: +86-10-64807099. E-mail: wuyj{at}ioz.ac.cn.
Received January 6, 2009; accepted March 17, 2009
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Abstract |
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Neuropathy target esterase (NTE) is proven to act as a lysophospholipase (LysoPLA) in mice and phospholipase B (PLB) in cultured mammalian cells. In sensitive species, organophosphate (OP)–induced delayed neurotoxicity is initiated when NTE is inhibited by > 70% and then aged. It is hypothesized that homeostasis of phosphatidylcholine (PC) and/or lysophosphatidylcholine (LPC) in mice might be disrupted by the OPs since NTE and other phospholipases could be inhibited. To test this hypothesis, we treated mice using tri-o-cresyl phosphate (TOCP), which can inhibit and age NTE. Phenylmethylsulfonyl fluoride (PMSF), which inhibits NTE but cannot age, was used as a negative control. Effects on activity of NTE, LysoPLA, and PLB, the levels of PC, LPC, and glycerophosphocholine (GPC), and the aging of NTE in the brain, spinal cord, and sciatic nerve were examined. The results showed that the activities of NTE, NTE-LysoPLA, LysoPLA, NTE-PLB, and PLB were significantly inhibited in both TOCP- and PMSF-treated mice, and the inhibition of NTE and NTE-LysoPLA or NTE-PLB showed a high correlation coefficient. The NTE inhibited by TOCP was of the aged type, while nearly all NTE inhibited by PMSF was of the unaged type. Although the GPC level was remarkedly decreased, no significant change of PC and LPC levels was observed. However, the inhibition of these enzymes in mice by TOCP exhibited different characteristics from the TOCP-treated hens that we previously reported, which indicates that these enzymes were inhibited and then recovered more rapidly in mice than in hens. All results suggest that PC and LPC homeostasis was not disrupted in mice after exposure to TOCP. Differences in inhibition of NTE, LysoPLA, and PLB activities by TOCP between mice and hens may elucidate why these two species display different signs after exposure to the same neuropathic OPs.
Key Words: organophosphate; homeostasis; phosphatidylcholine; lysophosphatidylcholine; mouse; neuropathy target esterase.