Cellular function of neuropathy target esterase in lysophosphatidylcholine action - PubMed (original) (raw)
. 2008 Nov 1;232(3):376-83.
doi: 10.1016/j.taap.2008.07.015. Epub 2008 Jul 25.
Affiliations
- PMID: 18706436
- DOI: 10.1016/j.taap.2008.07.015
Cellular function of neuropathy target esterase in lysophosphatidylcholine action
Sarah C Vose et al. Toxicol Appl Pharmacol. 2008.
Abstract
Neuropathy target esterase (NTE) plays critical roles in embryonic development and maintenance of peripheral axons. It is a secondary target of some organophosphorus toxicants including analogs of insecticides and chemical warfare agents. Although the mechanistic role of NTE in vivo is poorly defined, it is known to hydrolyze lysophosphatidylcholine (LPC) in vitro and may protect cell membranes from cytotoxic accumulation of LPC. To determine the cellular function of NTE, Neuro-2a and COS-7 cells were transfected with a full-length human NTE-containing plasmid yielding recombinant NTE (rNTE). We find the same inhibitor sensitivity and specificity profiles for rNTE assayed with LPC or phenyl valerate (a standard NTE substrate) and that this correlation extends to the LPC hydrolases of human brain, lymphocytes and erythrocytes. All of these LPC hydrolases are therefore very similar to each other in respect to a conserved inhibitor binding site conformation. NTE is expressed in brain and lymphocytes and contributes to LPC hydrolase activities in these tissues. The enzyme or enzymes responsible for erythrocyte LPC hydrolase activity remain to be identified. We also show that rNTE protects Neuro-2a and COS-7 cells from exogenous LPC cytotoxicity. Expression of rNTE in Neuro-2a cells alters their phospholipid balance (analyzed by liquid chromatography-mass spectrometry with single ion monitoring) by lowering LPC-16:0 and LPC-18:0 and elevating glycerophosphocholine without a change in phosphatidylcholine-16:0/18:1 or 16:0/18:2. NTE therefore serves an important function in LPC homeostasis and action.
Similar articles
- The homeostasis of phosphatidylcholine and lysophosphatidylcholine was not disrupted during tri-o-cresyl phosphate-induced delayed neurotoxicity in hens.
Hou WY, Long DX, Wang HP, Wang Q, Wu YJ. Hou WY, et al. Toxicology. 2008 Oct 30;252(1-3):56-63. doi: 10.1016/j.tox.2008.07.061. Epub 2008 Aug 5. Toxicology. 2008. PMID: 18755237 - Neuropathy target esterase: an essential enzyme for neural development and axonal maintenance.
Chang PA, Wu YJ. Chang PA, et al. Int J Biochem Cell Biol. 2010 May;42(5):573-5. doi: 10.1016/j.biocel.2009.12.007. Epub 2009 Dec 16. Int J Biochem Cell Biol. 2010. PMID: 20006730 Review. - Lysophosphatidylcholine hydrolases of human erythrocytes, lymphocytes, and brain: sensitive targets of conserved specificity for organophosphorus delayed neurotoxicants.
Vose SC, Holland NT, Eskenazi B, Casida JE. Vose SC, et al. Toxicol Appl Pharmacol. 2007 Oct 1;224(1):98-104. doi: 10.1016/j.taap.2007.06.008. Epub 2007 Jun 27. Toxicol Appl Pharmacol. 2007. PMID: 17663017 Free PMC article. - Neuropathy target esterase.
Glynn P. Glynn P. Biochem J. 1999 Dec 15;344 Pt 3(Pt 3):625-31. Biochem J. 1999. PMID: 10585848 Free PMC article. Review.
Cited by
- Activity-based protein profiling of organophosphorus and thiocarbamate pesticides reveals multiple serine hydrolase targets in mouse brain.
Nomura DK, Casida JE. Nomura DK, et al. J Agric Food Chem. 2011 Apr 13;59(7):2808-15. doi: 10.1021/jf101747r. Epub 2010 Jul 21. J Agric Food Chem. 2011. PMID: 21341672 Free PMC article. - The Catalytic Domain of Neuropathy Target Esterase Influences Lipid Droplet Biogenesis and Lipid Metabolism in Human Neuroblastoma Cells.
He L, Huang F, Wang Y, Wu Y, Xu L, Chang P. He L, et al. Metabolites. 2022 Jul 12;12(7):637. doi: 10.3390/metabo12070637. Metabolites. 2022. PMID: 35888761 Free PMC article. - Spg20-/- mice reveal multimodal functions for Troyer syndrome protein spartin in lipid droplet maintenance, cytokinesis and BMP signaling.
Renvoisé B, Stadler J, Singh R, Bakowska JC, Blackstone C. Renvoisé B, et al. Hum Mol Genet. 2012 Aug 15;21(16):3604-18. doi: 10.1093/hmg/dds191. Epub 2012 May 22. Hum Mol Genet. 2012. PMID: 22619377 Free PMC article. - Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms.
Fink JK. Fink JK. Acta Neuropathol. 2013 Sep;126(3):307-28. doi: 10.1007/s00401-013-1115-8. Epub 2013 Jul 30. Acta Neuropathol. 2013. PMID: 23897027 Free PMC article. Review. - Constructs of human neuropathy target esterase catalytic domain containing mutations related to motor neuron disease have altered enzymatic properties.
Hein ND, Stuckey JA, Rainier SR, Fink JK, Richardson RJ. Hein ND, et al. Toxicol Lett. 2010 Jul 1;196(2):67-73. doi: 10.1016/j.toxlet.2010.03.1120. Epub 2010 Apr 9. Toxicol Lett. 2010. PMID: 20382209 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials