Studies on the role of neurotoxic esterase in organophosphorous compound-induced delayed neurotoxicity
Neurotoxic esterase (NTE) is a protein with esterase activity that is proposed to be the site at which organophosphorus compound (OP) induced delayed neurotoxicity (OPIDIN) is initiated. The role of NTE in OPIDIN in unknown. The studies described in this dissertation were designed to further elucidate potential mechanisms underlying the involvement of NTE in OPIDN. The prophylactic effect of phenylmethylsulfonyl fluoride (PMSF) was found to be correlated with the time course of inhibition of NTE by PMSF and two neurotoxic OPs, and is therefore most likely to be due to the prevention of the binding of the OP to the initiation site. A membrane bound protein labelled with /sup 3/H-diisopropyl phosphorofluoridate (DiFP) with an apparent molecular weight of 160 K was the major binding site with a specificity similar to that of NTE. Recovery of NTE activity following in vivo inhibition by DiFP was found to be slower in hen brain when compared to chicks or rats. Differences in recovery in peripheral nerve were not found to be correlated with differences in susceptibility between species or between young and adult animals. The anterograde transport rate for NTE was estimated to be about 300 mm/day. Since exchange between mobile and stationary transport pools appeared to be rapid, it is concluded that the proximodistal delay in NTE recovery is due to a dilution of newly synthesized NTE by inhibited NTE as it is transported down the nerve.
- Research Organization:
- Duke Univ., Durham, NC (USA)
- OSTI ID:
- 5562474
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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ESTERASES
BIOCHEMISTRY
ORGANIC PHOSPHORUS COMPOUNDS
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CHICKENS
MOLECULAR WEIGHT
RATS
SCIATIC NERVE
TRITIUM COMPOUNDS
ANIMALS
BIRDS
BODY
CENTRAL NERVOUS SYSTEM
CHEMISTRY
ENZYMES
FOWL
HYDROLASES
LABELLED COMPOUNDS
MAMMALS
NERVES
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ORGANIC COMPOUNDS
ORGANS
RODENTS
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550201* - Biochemistry- Tracer Techniques