Gupta R P, Abou-Donia M B
Duke University Medical Center, Department of Pharmacology, Durham, North Carolina.
Neurochem Res. 1994 Apr;19(4):435-44. doi: 10.1007/BF00967321.
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.
二异丙基氟磷酸酯(DFP)在敏感物种中会引发有机磷酸酯诱导的迟发性神经毒性(OPIDN)。我们研究了DFP在体内和体外对母鸡脑微管蛋白聚合的影响。给母鸡单次注射DFP(1.7 mg/kg,皮下注射),18 - 21天后处死。来自DFP处理过的母鸡大脑的微管蛋白在聚合速率上显示出微小但显著的下降(14.42%),并且在30分钟内340 nm处的吸光度增加量下降了11.05%。DFP的体内处理还导致大脑上清液中tau浓度降低以及两种肽(45 kDa、35 kDa)浓度升高。这些肽似乎是微管相关蛋白2(MAP - 2)的降解产物。处理过的母鸡脑微管蛋白聚合速率的下降与神经化学改变以及OPIDN中这些丝状结构的局灶性变性和聚集是一致的。