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Functional Evaluation of Biological Neurotoxins in Networked Cultures of Stem Cell-derived Central Nervous System Neurons
Published on: February 5, 2015
Neuropathy target esterase inhibition by organophosphorus esters in human neuroblastoma cells
M Ehrich1, L Correll, B Veronesi
1Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg 24061.
Abstract:
Certain organophosphorus compounds (OPs) produce a delayed neuropathy (OPIDN) in man and some animal species. Capability to cause OPIDN is generally predicted in animal models by early and irreversible inhibition of neuropathy target esterase (NTE, neurotoxic esterase). In this study, NTE inhibition in response to OP exposure was examined in cell culture, using the human SH-SY5Y neuroblastoma cell line. Cells were exposed for 1 hr to equimolar (1 x 10(-5) M) concentrations of 6 OPs associated with OPIDN in vivo (including 2 protoxicants and 4 active (-P = O) toxicants), and 8 OPs that do not produce delayed neuropathy in animal models (including 5 protoxicants and 3 -P = O compounds). The -P = O compounds that cause OPIDN in animal models inhibited NTE > 60% at the test concentration; -P = O compounds that do not cause OPIDN in animal models inhibited NTE < 30%. Protoxicants did not inhibit NTE at the test concentration, reflecting their limited metabolism in the human cell line. These results indicate that human neuroblastoma cells have potential use in the initial screening of bioactive OPs with capability for causing OPIDN.
Insights
Organophosphorus compounds (OPs) causing delayed neuropathy inhibit neurotoxic esterase (NTE). Human neuroblastoma cells show potential for screening OPs
Area of Science:
- Neurotoxicology
- Biochemistry
- Cell Biology
Background:
- Organophosphorus compounds (OPs) can induce organophosphorus compound-induced delayed neuropathy (OPIDN) in humans and animals.
- Predicting OPIDN typically involves assessing the inhibition of neuropathy target esterase (NTE) in animal models.
- A reliable cell-based assay for screening OPIDN potential is needed.
Purpose of the Study:
- To investigate the utility of human neuroblastoma cells (SH-SY5Y) for evaluating NTE inhibition by OPs.
- To determine if NTE inhibition in cell culture correlates with OPIDN potential observed in vivo.
Main Methods:
- Exposure of human SH-SY5Y neuroblastoma cells to equimolar concentrations of various OPs.
- Categorization of OPs into those known to cause OPIDN in vivo and those that do not.
- Measurement of NTE inhibition in cells following OP exposure.
Main Results:
- OPs causing OPIDN in vivo significantly inhibited NTE (>60%) in the cell line.
- OPs not causing OPIDN showed minimal NTE inhibition (<30%) in the cell line.
- Protoxic OPs exhibited limited NTE inhibition, indicating low metabolism in this human cell line.
Conclusions:
- Human SH-SY5Y neuroblastoma cells effectively model NTE inhibition by OPs.
- This cell-based assay shows promise for the initial screening of OPs for their potential to cause OPIDN.
- The findings support the use of this in vitro system for predicting neurotoxicity of organophosphorus compounds.
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