Alteration in neurofilament axonal transport in the sciatic nerve of the diisopropyl phosphorofluoridate (DFP)-treated hen

被引:23
作者
Gupta, RP [1 ]
AbdelRahman, A [1 ]
Wilmarth, KW [1 ]
AbouDonia, MB [1 ]
机构
[1] DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27708
关键词
neurofilament proteins; diisopropyl phosphorofluoridate; hen; axonal transport; tubulin; OPIDN;
D O I
10.1016/S0006-2952(97)00002-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester that produces organophosphorus ester-induced delayed neurotoxicity (OPIDN) in hens 7-14 days after a single s.c. dose of 1.7 mg/kg. In this study, hens were treated with a single dose of DFP (1.7 mg/kg, s.c.) 24 hr after [S-35]methionine injection into the sacrolumbar region of their spinal cord, and killed 3, 7, 14, or 27 days post-DFP treatment. The rates of transport of labeled high (NF-H), medium (NF-M), and row (NF-L) molecular weight neurofilaments, and tubulin were faster in DFP-treated birds than in controls after 3 days. Subsequently, the rate of transport of these proteins started falling, so that the peaks of labeled proteins in control and DFP-treated hens were overlapping after 7 days. At 14 days, the peaks of NF-H, NF-M, and NF-L in treated hens were distinctly behind the corresponding peaks in control hens. This was again followed by an increase in transport of NF-H and NF-L, but not of NF-M, so that the labeled NF-H and NF-L showed the same pattern in control and treated hens after 27 days. The transient decrease in NF-H and NF-L axonal transport rate, and recovery correlated in a temporal manner with the previously reported increase of Ca2+/calmodulin-defendent protein kinase-mediated phosphorylation of neurofilament proteins and inhibition of calpain activity in the sciatic nerve in OPIDN. Proteinase inhibition has been reported recently to result in enhanced phosphorylation of neurofilaments in some cells. The present study suggests that the enhanced phosphorylation of neurofilaments by DFP-increased Ca2+/carmodulin-defendent protein kinase activity may be contributing toward alteration in NF axonal transport and the development of OPIDN. (C) 1997 Elsevier Science Inc.
引用
收藏
页码:1799 / 1806
页数:8
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