Tricresyl phosphate inhibits the formation of axon-like processes and disrupts neurofilaments in cultured mouse N2a and rat PC12 cells.
Tricresyl phosphate (1 microg/ml) inhibited the outgrowth of axon-like processes in mouse N2a neuroblastoma and rat PC12 pheochromocytoma cell lines induced to differentiate by serum withdrawal and nerve growth factor addition, respectively. By contrast, it had no effect on the outgrowth of processes by rat C6 glioma cells induced to differentiate with sodium butyrate. The effect on axon outgrowth in the two neuronal cell lines correlated with altered distribution of neurofilament proteins, as determined by indirect immunofluorescence with monoclonal antibody RMd09. Western blots of neuronal cell extracts probed with the same antibody revealed decreased cross-reactivity after exposure to tricresyl phosphate. The results suggest that tricresyl phosphate has a selective effect on neuronal cell differentiation, which involves impaired axon outgrowth, reduced levels of the neurofilament heavy chain and disruption of the neurofilament network.
Flaskos
J
J
Laboratory of Biochemistry and Toxicology, Faculty of Veterinary Medicine, University of Thessaloniki, Greece.
McLean
W G
WG
Fowler
M J
MJ
Hargreaves
A J
AJ
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002457:Cell Extracts / Q000737:chemistry; D019084:Fluorescent Antibody Technique, Indirect; D007202:Indicators and Reagents; D051379:Mice; D016900:Neurofilament Proteins / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D012394:Rosaniline Dyes; D014317:Tritolyl Phosphates / Q000494:pharmacology*
D002457:Cell Extracts; D007202:Indicators and Reagents; D016900:Neurofilament Proteins; D009498:Neurotoxins; D012394:Rosaniline Dyes; D014317:Tritolyl Phosphates; C048139:Coomassie blue