Relative Inhibitory Potencies of Chlorpyrifos Oxon, Chlorpyrifos Methyl Oxon, and Mipafox for Acetylcholinesterase Versus Neuropathy Target Esterase

Kropp, Timothy J.; Richardson, Rudy J.

doi:10.1080/15287390306360

Cited by 31 publications

(25 citation statements)

References 30 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CHM and CPF have been recently shown to have similar relative enzyme inhibitory potencies for acetylcholinesterase versus NTE and similar abilities to cause OPIDN (Kropp and Richardson 2003). Our present data suggest that, in serum withdrawal-mediated axonal outgrowth in N2a cells in vitro, there exists a similar pattern of effects for the two OPs at a molecular level.…”

Section: Proposed Mechanism Of Toxicitysupporting

confidence: 65%

Effects of Chlorpyrifos and Chlorpyrifos-Methyl on the Outgrowth of Axon-Like Processes, Tubulin, and GAP-43 in N2a Cells

Sachana

Flaskos

Hargreaves

2005

Toxicology Mechanisms and Methods

View full text Add to dashboard Cite

show abstract

Section: Proposed Mechanism Of Toxicitysupporting

confidence: 65%

Effects of Chlorpyrifos and Chlorpyrifos-Methyl on the Outgrowth of Axon-Like Processes, Tubulin, and GAP-43 in N2a Cells

Sachana

Flaskos

Hargreaves

2005

Toxicology Mechanisms and Methods

View full text Add to dashboard Cite

show abstract

“…An adaptation of the colorimetric assay of Johnson (1977) as modified by Kayyali et al (1991) and Kropp and Richardson (2003) was used. A 112.5 μL aliquot of sonicated fibroblasts was preincubated for 20 min at 37 °C with either 12.5 μL of 400 μM paraoxon to inhibit background esterase activity or 12.5 μL of 400 μM paraoxon plus 500 μM mipafox to inhibit background and NTE activity.…”

Section: Methodsmentioning

confidence: 99%

Motor neuron disease due to neuropathy target esterase mutation: Enzyme analysis of fibroblasts from human subjects yields insights into pathogenesis

et al. 2010

View full text Add to dashboard Cite

Recently, we identified neuropathy target esterase (NTE) mutation as the cause of an autosomal recessive motor neuron disease (NTE-MND). Subsequently, we showed that NTE-MND mutations reduced specific activity (SA) and altered inhibitory kinetics of NTE catalytic domain constructs. Recent preliminary results showed that NTE is expressed in cultured human skin fibroblasts, and others have used mutant forms of neuronal proteins expressed in fibroblasts as biomarkers of neurogenetic diseases. Therefore, the present study was carried out to test the hypothesis that NTE in cultured skin fibroblasts from NTE-MND subjects also exhibit altered enzymological properties assessed by SA and IC50 values of mipafox (MIP) and chlorpyrifos oxon (CPO). NTE SA was reduced to 65% of control (wild type NTE from commercially obtained fibroblasts) in homozygous M1012V fibroblasts and 59-61% of control in compound heterozygous R890H/c2946_2947InsCAGC fibroblasts. MIP IC50 values were unaffected by the NTE mutations, but the CPO IC50 increased 4.5-fold in homozygous M1012V fibroblasts. Interestingly, markedly reduced NTE SAs (40-43% of control) were observed in fibroblasts from asymptomatic subjects heterozygous for NTE insertion c2946_2947InsCAGC. This insertion is predicted to produce truncated NTE missing the last 235 residues of its catalytic domain. These observations confirm that NTE-MND mutations reduce NTE SA in vitro. Moreover, to the extent observations made in cultured fibroblasts may be generalized to events in the nervous system, lack of correlation between reduced fibroblast NTE SA and the occurrence of NTE-MND in NTE insertion mutation heterozygotes indicates that reduction of NTE SA alone is insufficient to cause MND.

show abstract

“…One criterion by which OP compounds that induce OPIDN differ from OPs that induce acute toxicity is their potency as inhibitors of AChE and neurotoxic esterase (NTE) (Kropp & Richardson, 2003). Differential toxicity of OPs has been compared in hen brain cell homogenates (Barber et al, 1999) and in mouse and human neuroblastoma cell cultures (Veronesi & Ehrich, 1993;Ehrich et al, 1997;Fowler et al, 2001).…”

mentioning

confidence: 99%

Neurofilament 200 as an Indicator of Differences Between Mipafox and Paraoxon Sensitivity in SY5Y Neuroblastoma Cells

Cho

Tiffany‐Castiglioni

2004

Journal of Toxicology and Environmental Health, Part A

View full text Add to dashboard Cite

Organophosphorus (OP) compounds produce potent neurotoxic effects in humans, including organophosphorus-induced delayed neuropathy (OPIDN). This investigation examined the potential for the 200-kD neurofilament protein (NF200) and other neuronal proteins to serve as indicators for neurite damage in a differentiated SY5Y human neuroblastoma cell culture system. Mipafox, which induces OPIDN, increased NF200 protein expression in SY5Y cells differentiated with human recombinant beta-nerve growth factor (NGF, 20 ng/ml) in a concentration-dependent manner, compared to NGF controls, when SY5Y cells were exposed to 0.3 or 30 microM mipafox during the last 5 days of neurite extension (experimental set A). However, mipafox produced little change in NF200 protein expression in SY5Y cells exposed continuously throughout neurite elongation (experimental set B). Paraoxon (up to 30 microM), which does not produce OPIDN, did not produce any change in NF200 expression in set A or set B. The upregulation of NF200 by mipafox may represent a compensatory response to neurite degeneration. Two other neuronal proteins, growth-associated protein 43 (GAP43) and microtubule-associated protein 2ab (MAP2ab), showed no changes in response to OP treatment in NGF-treated cells. Protein expression of NF200 was shown to be an indicator by which the sensitivities of SY5Y cells to mipafox and paraoxon were distinguishable at the molecular level. These results indicate an alternative approach and test system for investigating structure-activity relationships of OPs.

show abstract

Relative Inhibitory Potencies of Chlorpyrifos Oxon, Chlorpyrifos Methyl Oxon, and Mipafox for Acetylcholinesterase Versus Neuropathy Target Esterase

Cited by 31 publications

References 30 publications

Effects of Chlorpyrifos and Chlorpyrifos-Methyl on the Outgrowth of Axon-Like Processes, Tubulin, and GAP-43 in N2a Cells

Effects of Chlorpyrifos and Chlorpyrifos-Methyl on the Outgrowth of Axon-Like Processes, Tubulin, and GAP-43 in N2a Cells

Motor neuron disease due to neuropathy target esterase mutation: Enzyme analysis of fibroblasts from human subjects yields insights into pathogenesis

Neurofilament 200 as an Indicator of Differences Between Mipafox and Paraoxon Sensitivity in SY5Y Neuroblastoma Cells

Contact Info

Product

Resources

About