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Partial characterization of neuropathy target esterase and related phenyl valerate esterases from bovine adrenal
M A Sogorb1, S Viniegra, J A Reig
1Department of Neurochemistry, University of Alicante, Spain.
Abstract:
The mechanism by which organophosphorus-induced delayed polyneuropathy is induced relates to the specific inhibition and subsequent modification ("aging") of a protein known as neuropathy target esterase (NTE), operatively defined as paraoxon-resistant and mipafox-sensitive phenyl valerate (PV) esterase activity. This protein has fundamentally been investigated in hen brain, the latter being the habitually employed OPIDP study model. In the present article, a partial characterization is made of the NTE and other related PV esterases in the bovine adrenal medulla and brain; NTE sensitivity to the neurotoxic organophosphorus compound mipafox is investigated, and its subcellular distribution is studied. The NTE activity of the adrenal medulla was found to be the highest of those among the tissues studied to date (5000 +/- 1400 mU/g tissue; +/- SD, n = 12). This activity represented 93% of the PV esterase activity resistant to 40 microM paraoxon in the particulate fraction of the adrenal medulla and approximately 50% of total PV esterase activity. In the bovine brain, these proportions were 72 and 26%, respectively, i.e., similar to those described in hen brain. The mipafox inhibition curve of PV esterase activity resistant to 40 microM paraoxon in the particulate fraction of the adrenal medulla suggests that NTE activity fundamentally comprises a mipafox-sensitive component with an I50 of 6.39 microM at 30 minutes, which is similar to the value reported in hen brain. NTE activity in the bovine adrenal medulla is almost exclusively limited to the particulate fraction, the microsomal fraction, plasma membrane, and chromaffin granule-enriched fractions being the highest in terms of specific activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Organophosphorus-induced delayed polyneuropathy involves neuropathy target esterase (NTE) modification. Bovine adrenal medulla exhibits high NTE activity, similar to hen brain, suggesting its role in neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Organophosphorus-induced delayed polyneuropathy (OPIDP) is linked to neuropathy target esterase (NTE) inhibition and aging.
- NTE is typically studied in hen brain, the established model for OPIDP research.
- Understanding NTE in other species and tissues is crucial for a comprehensive view of neurotoxic mechanisms.
Purpose of the Study:
- To partially characterize NTE and related phenyl valerate (PV) esterases in bovine adrenal medulla and brain.
- To investigate NTE sensitivity to the neurotoxic organophosphorus compound mipafox.
- To determine the subcellular distribution of NTE in bovine tissues.
Main Methods:
- Assay of paraoxon-resistant and mipafox-sensitive phenyl valerate (PV) esterase activity.
- Characterization of NTE activity in bovine adrenal medulla and brain tissue fractions.
- Determination of mipafox inhibition kinetics and NTE subcellular localization.
Main Results:
- Bovine adrenal medulla displayed the highest NTE activity (5000 +/- 1400 mU/g tissue), representing 93% of paraoxon-resistant PV esterase in the particulate fraction.
- Bovine brain showed similar NTE proportions (72% resistant, 26% total) to hen brain.
- NTE in bovine adrenal medulla is mipafox-sensitive (I50 = 6.39 microM), primarily located in the particulate fraction, including microsomes, plasma membrane, and chromaffin granules.
Conclusions:
- The bovine adrenal medulla possesses significant NTE activity, comparable to hen brain, indicating its potential role in neurotoxicity.
- NTE in bovine adrenal medulla exhibits characteristics similar to those in hen brain, including mipafox sensitivity and subcellular distribution.
- These findings contribute to understanding the biochemical basis of OPIDP and highlight the adrenal medulla as a key tissue for NTE research.