Inhibition of neurite outgrowth in differentiating mouse N2a neuroblastoma cells by phenyl saligenin phosphate: Effects on MAP kinase (ERK 1/2) activation, neurofilament heavy chain phosphorylation and neuropathy target esterase activity

Hargreaves, A.J. ORCID: 0000-0001-9754-5477, Fowler, M.J., Sachana, M., Flaskos, J., Bountouri, M., Coutts, I.C., Glynn, P., Harris, W. and Mclean, W.G., 2006. Inhibition of neurite outgrowth in differentiating mouse N2a neuroblastoma cells by phenyl saligenin phosphate: Effects on MAP kinase (ERK 1/2) activation, neurofilament heavy chain phosphorylation and neuropathy target esterase activity. Biochemical Pharmacology, 71 (8), pp. 1240-1247. ISSN 0006-2952

[img]
Preview
Text
195951_48 Hargreaves PostPrint.pdf

Download (290kB) | Preview

Abstract

Sub-lethal concentrations of the organophosphate phenyl saligenin phosphate (PSP) inhibited the outgrowth of axon-like processes in differentiating mouse N2a neuroblastoma cells (IC50 2.5 μM). A transient rise in the phosphorylation state of neurofilament heavy chain (NFH) was detected on Western blots of cell extracts treated with 2.5 μM PSP for 4 h compared to untreated controls, as determined by a relative increase in reactivity with monoclonal antibody Ta51 (anti-phosphorylated NFH) compared to N52 (anti-total NFH). However, cross-reactivity of PSP-treated cell extracts was lower than that of untreated controls after 24 h exposure, as indicated by decreased reactivity with both antibodies. Indirect immunofluorescence analysis with these antibodies revealed the appearance of neurofilament aggregates in the cell bodies of treated cells and reduced axonal staining compared to controls. By contrast, there was no significant change in reactivity with anti-a tubulin antibody B512 at either time point. The activation state of the MAP kinase ERK 1/2 increased significantly after PSP treatment compared to controls, particularly at 4 h, as indicated by increased reactivity with monoclonal antibody E-4 (anti-phosphorylated MAP kinase) but not with polyclonal antibody K-23 (anti-total MAP kinase). The observed early changes were concomitant with almost complete inhibition of the activity of neuropathy target esterase (NTE), one of the proposed early molecular targets in organophosphate-induced delayed neuropathy (OPIDN).

Item Type: Journal article
Description: Post-print
Publication Title: Biochemical Pharmacology
Creators: Hargreaves, A.J., Fowler, M.J., Sachana, M., Flaskos, J., Bountouri, M., Coutts, I.C., Glynn, P., Harris, W. and Mclean, W.G.
Date: 2006
Volume: 71
Number: 8
ISSN: 0006-2952
Identifiers:
NumberType
10.1016/j.bcp.2006.01.008DOI
Rights: Copyright © 2006 Elsevier
Divisions: Schools > School of Science and Technology
Depositing User: EPrints Services
Date Added: 09 Oct 2015 09:45
Last Modified: 09 Jun 2017 13:10
URI: http://irep.ntu.ac.uk/id/eprint/2355

Actions (login required)

Edit View Edit View

Views

Views per month over past year

Downloads

Downloads per month over past year