Partial characterization of neuropathy target esterase and related phenyl valerate esterases from bovine adrenal medulla

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)

Analysis of the neurotoxic effects of neuropathic organophosphorus compounds in adult zebrafish

“…DFP is a neurotoxin analog of the chemical warfare agents sarin and soman and has a potent inhibitory effect on NTE 53 , 55 . The proportion of PV-NTE activity was 6% of total PVase activity determined in this study in zebrafish brain, and the absolute value in term of activity per gram tissue, is approximately 10-fold lower than that reported for hen brain 56 but was nonetheless within the same unit range and similar to that observed in hen peripheral nerve, and much lower than that in adrenal medulla chromaffin cells as that is the tissue with higher NTE content that has been reported 57 . As described in mammalian models and hens, zebrafish NTE inhibition by both compounds was dose- and time-dependent.…”

Neuropathy Target Esterase

“…Relatively high levels of NTE have been found in several nonneural chicken tissues, including intestine, spleen, and thymus (Johnson, 1982a), as well as circulating lymphocytes (Dudek and Richardson, 1982). Extremely high levels have been found in bovine adrenal medulla (Sogorb et al, 1994). Cultured bovine chromaffin cells and human neuroblastoma cell lines have been shown to have substantial NTE activity and have been suggested as in vitro systems for assessment of neuropathic OP compounds Veronesi et al, 1997).…”