Abstract
Neuropathy target esterase (NTE) is a membrane-bound carboxylesterase activity that has been proposed as the target site for initiation of organophosphate-induced delayed neuropathy. This activity is identified by its resistance to treatment with Paraoxon and sensitivity to co-incubation with Paraoxon and Mipafox. Sucrose-density-gradient centrifugation of membrane-associated proteins isolated from chick-embryo brains identified three proteins, Mr 161,000, 116,500 and 103,000, that were labelled with [3H]di-isopropyl phosphorofluoridate in an NTE-like manner and that co-migrated with NTE. The 161,000-Mr and 116,500-Mr proteins were identified in both adult and embryo brain. One or both of these proteins may therefore contribute to the activity defined as NTE. In addition, a 61,000-Mr protein was identified that does not comigrate with NTE, but that was labelled with [3H]di-isopropyl phosphorofluoridate in a Paraoxon-resistant and Mipafox-sensitive manner. The effect of Mipafox on labelling, however, was reversibly blocked by co-incubation with Paraoxon. This protein, therefore, is not NTE, but has the necessary inhibitor-sensitivity to be the target site for organophosphate-induced delayed neuropathy.
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- BEERS R. F., Jr, SIZER I. W. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 1952 Mar;195(1):133–140. [PubMed] [Google Scholar]
- CAVANAGH J. B. PERIPHERAL NERVE CHANGES IN ORTHO-CRESYL PHOSPHATE POISONING IN THE CAT. J Pathol Bacteriol. 1964 Apr;87:365–383. doi: 10.1002/path.1700870217. [DOI] [PubMed] [Google Scholar]
- CAVANAGH J. B. The toxic effects of triortho-cresyl phosphate on the nervous system; an experimental study in hens. J Neurol Neurosurg Psychiatry. 1954 Aug;17(3):163–172. doi: 10.1136/jnnp.17.3.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carrington C. D., Abou-Donia M. B. Characterization of [3H]di-isopropyl phosphorofluoridate-binding proteins in hen brain. Rates of phosphorylation and sensitivity to neurotoxic and non-neurotoxic organophosphorus compounds. Biochem J. 1985 Jun 15;228(3):537–544. doi: 10.1042/bj2280537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carrington C. D., Abou-Donia M. B. Paraoxon reversibly inhibits neurotoxic esterase. Toxicol Appl Pharmacol. 1985 Jun 15;79(1):175–178. doi: 10.1016/0041-008x(85)90380-1. [DOI] [PubMed] [Google Scholar]
- Clothier B., Johnson M. K. Rapid aging of neurotoxic esterase after inhibition by di-isopropyl phosphorofluoridate. Biochem J. 1979 Feb 1;177(2):549–558. doi: 10.1042/bj1770549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DAVISON A. N. Some observations on the cholinesterases of the central nervous system after the administration of organo-phosphorus compounds. Br J Pharmacol Chemother. 1953 Jun;8(2):212–216. doi: 10.1111/j.1476-5381.1953.tb00781.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis C. S., Richardson R. J. Neurotoxic esterase: characterization of the solubilized enzyme and the conditions for its solubilization from chicken brain microsomal membranes with ionic, zwitterionic, or nonionic detergents. Biochem Pharmacol. 1987 May 1;36(9):1393–1399. doi: 10.1016/0006-2952(87)90104-3. [DOI] [PubMed] [Google Scholar]
- Dudek B. R., Richardson R. J. Evidence for the existence of neurotoxic esterase in neural and lymphatic tissue of the adult hen. Biochem Pharmacol. 1982 Mar 15;31(6):1117–1121. doi: 10.1016/0006-2952(82)90351-3. [DOI] [PubMed] [Google Scholar]
- Fairbanks G., Steck T. L., Wallach D. F. Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane. Biochemistry. 1971 Jun 22;10(13):2606–2617. doi: 10.1021/bi00789a030. [DOI] [PubMed] [Google Scholar]
- Ishikawa Y., Chow E., McNamee M. G., McChesney M., Wilson B. W. Separation of paraoxon and mipafox sensitive esterases by sucrose density gradient sedimentation. Toxicol Lett. 1983 Jul;17(3-4):315–320. doi: 10.1016/0378-4274(83)90244-8. [DOI] [PubMed] [Google Scholar]
- Johnson M. K. A phosphorylation site in brain and the delayed neurotoxic effect of some organophosphorus compounds. Biochem J. 1969 Feb;111(4):487–495. doi: 10.1042/bj1110487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson M. K. Improved assay of neurotoxic esterase for screening organophosphates for delayed neurotoxicity potential. Arch Toxicol. 1977 Jun 18;37(2):113–115. doi: 10.1007/BF00293860. [DOI] [PubMed] [Google Scholar]
- Johnson M. K. Organophosphorus and other inhibitors of brain 'neurotoxic esterase' and the development of delayed neurotoxicity in hens. Biochem J. 1970 Dec;120(3):523–531. doi: 10.1042/bj1200523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson M. K. The delayed neurotoxic effect of some organophosphorus compounds. Identification of the phosphorylation site as an esterase. Biochem J. 1969 Oct;114(4):711–717. doi: 10.1042/bj1140711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson M. K. The primary biochemical lesion leading to the delayed neurotoxic effects of some organophosphorus esters. J Neurochem. 1974 Oct;23(4):785–789. doi: 10.1111/j.1471-4159.1974.tb04404.x. [DOI] [PubMed] [Google Scholar]
- LEDERBERG J. The beta-d-galactosidase of Escherichia coli, strain K-12. J Bacteriol. 1950 Oct;60(4):381–392. doi: 10.1128/jb.60.4.381-392.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Lotti M., Caroldi S., Moretto A., Johnson M. K., Fish C. J., Gopinath C., Roberts N. L. Central-peripheral delayed neuropathy caused by diisopropyl phosphorofluoridate (DFP): segregation of peripheral nerve and spinal cord effects using biochemical, clinical, and morphological criteria. Toxicol Appl Pharmacol. 1987 Mar 30;88(1):87–96. doi: 10.1016/0041-008x(87)90272-9. [DOI] [PubMed] [Google Scholar]
- Peterson G. L. A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem. 1977 Dec;83(2):346–356. doi: 10.1016/0003-2697(77)90043-4. [DOI] [PubMed] [Google Scholar]
- Richardson R. J., Davis C. S., Johnson M. K. Subcellular distribution of marker enzymes and of neurotoxic esterase in adult hen brain. J Neurochem. 1979 Feb;32(2):607–615. doi: 10.1111/j.1471-4159.1979.tb00391.x. [DOI] [PubMed] [Google Scholar]
- Soliman S. A., Curley A. Assay of chicken brain neurotoxic esterase activity using leptophosoxon as the selective neurotoxic inhibitor. J Anal Toxicol. 1981 Jul-Aug;5(4):183–186. doi: 10.1093/jat/5.4.183. [DOI] [PubMed] [Google Scholar]
- Wang C., Smith R. L. Lowry determination of protein in the presence of Triton X-100. Anal Biochem. 1975 Feb;63(2):414–417. doi: 10.1016/0003-2697(75)90363-2. [DOI] [PubMed] [Google Scholar]
- Williams D. G., Johnson M. K. Gel-electrophoretic identification of hen brain neurotoxic esterase, labelled with tritiated di-isopropyl phosphorofluoridate. Biochem J. 1981 Nov 1;199(2):323–333. doi: 10.1042/bj1990323. [DOI] [PMC free article] [PubMed] [Google Scholar]
