Promotion of organophosphate-induced delayed polyneuropathy by phenylmethanesulfonyl fluoride

Lotti, Marcello; Caroldi, Stefano; Capodicasa, Eugenio; Moretto, Angelo

doi:10.1016/0041-008x(91)90114-t

Cited by 87 publications

(30 citation statements)

References 17 publications

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“…However, it has been shown recently that when PMSF or other non-ageable inhibitors are given after a neuropathic UP they promote OPIDP (Pope and Padilla 1990;Lotti et al 1991). Thus tar promotion was caused only by nonageable NTE inhibitors at doses which were inhibitory to NTE (when given to naive birds), and when about 30% of NTE was affected by the initiating UP .…”

Section: Introductionmentioning

confidence: 91%

Phenylmethanesulfonyl fluoride elicits and intensifies the clinical expression of neuropathic insults

et al. 1992

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It has been recently reported that phenylmethanesulfonyl fluoride (PMSF) when given to hens after a neuropathic organophosphate (OP) promotes organophosphate-induced delayed polyneuropathy (OPIDP). Chicks are resistant to OPIDP despite high inhibition/aging of neuropathy target esterase (NTE), the putative target of OPIDP initiation. However, when PMSF (300 mg/kg s.c.) is given to chicks after di-butyl 2,2-dichlorovinyl phosphate (DBDCVP, 1 or 5 mg/kg s.c.), OPIDP is promoted. Inhibition/aging of at least 30% of NTE was thought to be an essential prerequisite for promotion to be elicited in adult hens. However, we observed in hens that when NTE is maximally affected (greater than 90%) by phenyl N-methyl N-benzyl carbamate (40 mg/kg i.v.), a non-ageable inhibitor of NTE, and then PMSF is given (120 mg/kg/day s.c. x 3 days) clinical signs of neuropathy become evident. Methamidophos (50 mg/kg p.o. to hens), which produces in vivo a reactivatable form of inhibited NTE, was shown either to protect from or promote OPIDP caused by DBDCVP (0.45 mg/kg s.c.), depending on the sequence of dosing. Because very high doses of methamidophos cause OPIDP, we considered this effect to be a "self-promoted" OPIDP. We concluded that NTE inhibitors might have different intrinsic activities for producing OPIDP once NTE is affected. Aging might differentiate highly neuropathic OPs, like DBDCVP, from less neuropathic OPs, like methamidophos, or from the least neuropathic carbamates, which require promotion in order for neuropathy to be expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Introductionmentioning

confidence: 91%

Phenylmethanesulfonyl fluoride elicits and intensifies the clinical expression of neuropathic insults

et al. 1992

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“…c Maximal clinical score assessed 14-21 days after last dosing on a 0-8 point scale. DFP alone causes NTE inhibitions as follows: 81 ± 8, 84 ± 15, and 68 ± 15% in brain, spinal cord, and peripheral nerve, respectively (Lotti et al, 1991). None of the sulfonyl fluorides given alone caused neuropathy at maximum tested doses (data not shown).…”

Section: Chemicalsmentioning

confidence: 99%

Sulfonyl Fluorides and the Promotion of Diisopropyl Fluorophosphate Neuropathy

1996

Toxicol Sci

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Phenylmethanesulfonyl fluoride (PMSF) enhances the neuropathic response when given to hens after organophosphates causing delayed polyneuropathy. This study was undertaken to ascertain whether other sulfonyl fluorides promote diisopropyl fluorophosphate (DFP) neuropathy in hens and if they inhibit neuropathy target esterase (NTE), the target for organophosphateinduced delayed polyneuropathy. Among seven sulfonyl fluoride analogs of PMSF (alkyl-, and phenylsulfonyl fluorides), only nbutanesulfonyl fluoride was found to be an NTE inhibitor in vitro at a concentration (I50 = 60 //M) similar to that of PMSF. nButanesulfonyl fluoride (0.2 mmol • kg" 1 sc to hens) caused both NTE inhibition in nervous tissues (>80%) and promotion of neuropathy after DFP (0.003 mmol • kg" 1 sc) similar to those observed after the same molar dose of PMSF. These results confirm that, so far, all known promoters of organophosphate polyneuropathy are also NTE inhibitors, c 19% sod«y of Toi Diisopropyl fluorophosphate (DFP) and other organophosphorus esters (OPs) cause a central-peripheral axonal degeneration known as organophosphate-induced delayed polyneuropathy (OPIDP). The mechanism of OPIDP initiation is thought to involve high inhibition (>70%) of neuropathy target esterase (NTE) in nervous tissues. Certain sulfonyl fluorides, including phenylmethanesulfonyl fluoride (PMSF), prevent OPIDP when given prior to a neuropathic OP by sulfonylating at least 40-50% NTE. Initiation of and protection from OPIDP have been explained as occurring either through a molecular rearrangement of inhibited NTE, occurring with neuropathic inhibitors only (Johnson, 1990), or through differences in neuropathic power of inhibitors, being weak for protective and strong for neuropathic inhibitors (Lotti et ai, 1993). In either case, when enough NTE is sulfonylated, the subsequent phosphorylation by neuropathic OPs cannot initiate OPIDP.However, clinical and morphological signs of OPIDP are exacerbated when PMSF is given after neuropathic OPs (Pope and Padilla, 1990; Lotti et ai, 1991). Phosphinates (Johnson and Read, 1993) and carbamates (Lotti et ai, 1991) also exacerbate OPIDP. This effect was called promotion of OPIDP and was found to be unrelated to NTE inhibition (Moretto et ai, 1994).Thus, PMSF may cause both protection and promotion, in either case at doses which are inhibitory to NTE. When PMSF is given before a neuropathic OP, there is protection because NTE is sulphonylated and cannot be phosphorylated. Therefore, the effect on the (unknown) promotion site becomes irrelevant because neuropathy is not initiated. When PMSF is given after the neuropathic OP, promotion occurs because the neuropathy is initiated by organophosphorylation and PMSF then affects the promotion site.The purpose of this study was to ascertain whether sulfonyl fluorides other than PMSF are capable of promoting DFP neuropathy. We also determined their ability to inhibit NTE since all known promoters are NTE inhibitors and most of them promote neuropathy at doses which inhibit NT...

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“…As the enriched preparation of S-NTE2 comes from a peak in Sephacryl S-300 of~100 kDa molecular mass, the native protein is likely to be a dimer. It has recently been described that phenylmethylsulfonyl fluoride (PMSF), which is not a neuropathy inducer in its own right, can enhance OP neuropathy and other neurodegenerative disorders via a phenomenon called "promotion" (Lotti et al, 1991). The target of such promotion remains unknown.…”

Section: Although Two Apparent Soluble Nte Froms S-nte1mentioning

confidence: 99%

“…There is evidence that P-NTE is not directly involved, but the target of promotion should possess properties similar to those of P-NTE, because all known promoters are P-NTE inhibitors (Lotti et al, 1991;Aldridge, 1993;Moretto et al, 1994;Lotti, 1995). However, P-NTE (the usual NTE form assayed by most researchers) has been discarded as a potential target of the promotion effect induced by PMSF (Moretto et al, 1994); in this sense, it has been deduced that such a target should be an "NTE-like" protein (i.e., possessing a qualitatively similar response to mipafox) (Lotti et al, 1991). Therefore, this 56-kDa S-NTE2 protein, sensitive to both mipafox and S9B, is a good candidate for investigation both as a potential target of the neuropathy promotion effect (Lotti, 1996) and as the potential target of delayed neuropathy.…”

Section: Although Two Apparent Soluble Nte Froms S-nte1mentioning

confidence: 99%

Purification and Characterization of Naturally Soluble Neuropathy Target Esterase from Chicken Sciatic Nerve by HPLC and Western Blot

Escudero

Vilanova

1997

Journal of Neurochemistry

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Neuropathy target esterase (NTE) activity is defined operatively as the paraoxon-resistant mipafoxsensitive phenyl valerate esterase activity. A preparation containing a soluble isoform (S-NTE2) has been obtained from sciatic nerve. It was inhibited by the biotinylated organophosphorous ester S9B [1-(saligenincyclic phospho)-9-biotinyldiaminononane] in a progressive manner showing a second-order rate constant of (3.50 ±0.26) x 106 M 1 min~1with an l5for 30 mm of 6.6 ± 0.4 nM. S-NTE2 was enriched 218-fold by gel filtration followed by strong and weak anion-exchange chromatographies in HPLC. In western blots, this enriched sample showed two bands of endogenous biotinylated polypeptides after treating the blots with streptavidin-alkaline phosphatase complex. When the sample was treated with S9B, another biotinylated band was observed with a molecular mass of -~56kDa, which was not seen when the sample had been pretreated with mipafox before the S9B labeling. It was deduced that this band represents a polypeptide (identified as the S-NTE2 protein) that is bound by both mipafox and S9B and that should be responsible for the progressive S9B inhibition. It is possible that S-NTE2 is the target for attack by compounds that promote delayed neuropathy. Key Words: Neuropathy target esteraseOrganophosphorus-Soluble esterase-Sciatic nerve.

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Promotion of organophosphate-induced delayed polyneuropathy by phenylmethanesulfonyl fluoride

Cited by 87 publications

References 17 publications

Phenylmethanesulfonyl fluoride elicits and intensifies the clinical expression of neuropathic insults

Phenylmethanesulfonyl fluoride elicits and intensifies the clinical expression of neuropathic insults

Sulfonyl Fluorides and the Promotion of Diisopropyl Fluorophosphate Neuropathy

Purification and Characterization of Naturally Soluble Neuropathy Target Esterase from Chicken Sciatic Nerve by HPLC and Western Blot

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