Inhibition of neurite outgrowth in N2a cells by leptophos and carbaryl: effects on neurofilament heavy chain, GAP-43 and HSP-70.
The neurodegenerative properties of the organophosphate ester leptophos (LEP) and the carbamate ester carbaryl (CB), both of which can cause neuropathic effects in animals, were investigated in differentiating mouse N2a neuroblastoma cells. At a sublethal concentration of 3 microM, both LEP and CB were able to inhibit the outgrowth of axon-like processes from N2a cells after only 4 h of exposure. Extracts of cells exposed to LEP showed decreased cross-reactivities with monoclonal antibodies that recognise the neurofilament heavy chain (NFH) and the growth-associated protein GAP-43. However, they exhibited increased cross-reactivity with a monoclonal antibody that recognises the heat shock protein HSP-70. In contrast, no changes were noted in the levels of antibody binding in blots of extracts of cells exposed to CB. It is concluded that, although both LEP and CB inhibit the formation of axons in vitro, the early biochemical changes underlying the neurodegenerative effects of the two compounds are different.
Sachana
M
M
Laboratory of Biochemistry and Toxicology, Faculty of Veterinary Medicine, Aristotelian University of Thessaloniki, 546 06 Thessaloniki, Greece.
Flaskos
J
J
Alexaki
E
E
Hargreaves
A J
AJ
D000818:Animals; D000911:Antibodies, Monoclonal; D001369:Axons / Q000187:drug effects*; D012721:Carbaryl / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D007306:Insecticides / Q000009:adverse effects*; D010773:Leptophos / Q000009:adverse effects*; D051379:Mice; D009420:Nervous System / Q000187:drug effects / Q000473:pathology; D016501:Neurites / Q000187:drug effects*; D009447:Neuroblastoma / Q000473:pathology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018840:HSP70 Heat-Shock Proteins; D007306:Insecticides; D010773:Leptophos; D012721:Carbaryl