+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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): 1240-1247



Sub-lethal concentrations of the organophosphate phenyl saligenin phosphate (PSP) inhibited the outgrowth of axon-like processes in differentiating mouse N2a neuroblastoma cells (IC(50) 2.5 microM). A transient rise in the phosphorylation state of neurofilament heavy chain (NFH) was detected on Western blots of cell extracts treated with 2.5 microM 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-alpha-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).

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 012216226

Download citation: RISBibTeXText

PMID: 16499876

DOI: 10.1016/j.bcp.2006.01.008


Related references

Inhibition of neurite outgrowth in N2a cells by leptophos and carbaryl: Effects on neurofilament heavy chain, GAP-43 and HSP-70. Toxicology In Vitro 17(1): 115-120, 2003

Effects of organophosphate phenyl saligenin phosphate and polyether carboxylic ionophore lasalocid on motor nerve conduction velocity, neuropathy target esterase enzyme activity, and clinical ataxia in chickens. Toxicology Mechanisms and Methods 19(5): 351-355, 2009

Effects of avermectins on neurite outgrowth in differentiating mouse neuroblastoma N2a cells. Toxicology Letters 192(2): 206-211, 2010

Integrin alpha(1) beta(1)-mediated activation of cyclin-dependent kinase 5 activity is involved in neurite outgrowth and human neurofilament protein H Lys-Ser-Pro tail domain phosphorylation. Journal of Neuroscience 20(16): 6055-6062, 2000

The effects of tricresyl phosphate on axon outgrowth and neurofilament levels in mouse N2a neuroblastoma cells. Biochemical Society Transactions 25(4): S574, 1997

Overexpression of tau leads to the stimulation of neurite outgrowth, the activation of caspase 3 activity, and accumulation and phosphorylation of tau in neuroblastoma cells on cAMP treatment. Neuroscience Research 49(4): 363-371, 2004

Protein kinase C-epsilon is implicated in neurite outgrowth in differentiating human neuroblastoma cells. Cell Growth and Differentiation 7(6): 775-785, 1996

Increase in cytoplasmic casein kinase II-type activity accompanies neurite outgrowth after DNA synthesis inhibition in NIA-103 neuroblastoma cells. Journal of Neurochemistry 58(5): 1820-1828, 1992

Organophosphorus neuropathy target esterase inhibitors selectively block outgrowth of neurite-like and cell processes in cultured cells. Toxicology Letters 98(3): 139-146, 1998

Phenyl Saligenin Phosphate Induced Caspase-3 and c-Jun N-Terminal Kinase Activation in Cardiomyocyte-Like Cells. Chemical Research in Toxicology 28(11): 2179-2191, 2015

K-252a induces tyrosine phosphorylation of the focal adhesion kinase and neurite outgrowth in human neuroblastoma SH-SY5Y cells. Journal Of Neurochemistry. 64(2): 540-549, 1995

Neurite outgrowth from mouse neuroblastoma and cerebellar cells induced by the protein kinase inhibitor H-7. Neuroscience Letters 105(3): 241-245, 1989

Induction of neurite outgrowth in PC12 cells by a-phenyl-N-tert-butylnitron through activation of protein kinase C and the Ras-extracellular signal-regulated kinase pathway. The Journal of Biological Chemistry 276(35): 779-85, 2001