Actions of two highly potent organophosphorus neuropathy target esterase inhibitors in mammalian cell lines.
Neuropathy target esterase (NTE) is inhibited by many organophosphorus compounds that induce delayed neuropathy. This study examines two of the most potent NTE inhibitors, 2-octyl-4H-1,3,2-benzodioxaphosphorin 2-oxide (OBDPO) and ethyl octylphosphonofluoridate (EOPF), in cell lines with neural properties (PC-12 and NB41A3) and of nonneural origin (C6 and HeLa). NTE-like esteratic activity is higher in PC-12, HeLa and C6 cells than in NB41A3 cells and in each case is inhibited 50% by OBDPO and EOPF at 0.03-3.4 nM in vitro and by OBDPO at 0.080-36 nM in situ in culture. An NTE-like protein(s) of about 155 kDa is phosphorylated and labeled by [3H-octyl]OBDPO in these cell lines in the same order as their relative NTE esteratic activity. Cytotoxic levels of OBDPO and EOPF (300-500 microM) are generally 10(5) to > 10(7)-fold higher than required for NTE inhibition. PC-12 cells and OBDPO/[3H]OBDPO and EOPF are therefore suitable for research on non-lethal biochemical disruptions from NTE phosphorylation and aging.
Li
W
W
Department of Environmental Science, Policy and Management, University of California, Berkeley 94720-3112, USA.
Casida
J E
JE
D000818:Animals; D015415:Biomarkers; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002802:Cholinesterases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000633:toxicity*; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D051379:Mice; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology
C092561:2-octyl-4H-1,3,2-benzodioxaphosphorin-2-oxide; D015415:Biomarkers; D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; C100419:ethyl octylphosphonofluoridate; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D002802:Cholinesterases