In vivo and in vitro effects of diisopropyl phosphorofluoridate (DFP) on the rate of hen brain tubulin polymerization.
Diisopropyl phosphorofluoridate (DFP) produces organophosphorus ester-induced delayed neurotoxicity (OPIDN) in sensitive species. We have investigated the in vivo and in vitro effects of DFP on hen brain tubulin polymerization. Hens were treated with a single dose of DFP (1.7 mg/kg, sc.), and were sacrificed after 18-21 days. Tubulin from DFP-treated hen brains showed small but significant decrease (14.42%) in the rate of polymerization and 11.05% decrease in rise in O.D. at 340 nm in 30 min. DFP in vivo treatment also resulted in decreased concentration of tau and an enhanced concentration of two peptides (45 kDa, 35 kDa) in the brain supernatant. These peptides seemed to be the degradation products of MAP-2. The decrease in the rate of brain tubulin polymerization in treated hens is consistent with neurochemical alterations and the focal degeneration and aggregation of these filamentous structures in OPIDN.
Gupta
R P
RP
Duke University Medical Center, Department of Pharmacology, Durham, North Carolina.
Abou-Donia
M B
MB
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002122:Calcium Chloride / Q000494:pharmacology; D002417:Cattle; D002645:Chickens; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007531:Isoflurophate / Q000494:pharmacology*; D007700:Kinetics; D015636:Magnesium Chloride / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009994:Osmolar Concentration; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology; D014404:Tubulin / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D016875:tau Proteins / Q000032:analysis
D008869:Microtubule-Associated Proteins; D014404:Tubulin; D016875:tau Proteins; D015636:Magnesium Chloride; D007531:Isoflurophate; D012965:Sodium Chloride; D011189:Potassium Chloride; D002122:Calcium Chloride