Oxidative Glutathione Conjugation and Its Novel Role in Activation of the Organophosphorus Insecticide Prothiofos

Miyamoto, Toru; Mikawa, Tsuyoshi

doi:10.1584/jpestics.30.31

Cited by 5 publications

(3 citation statements)

References 13 publications

(11 reference statements)

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“…However, there is a growing body of evidences that GSTs also play an important role in OP detoxification [51]. The action of GSTs on OP insecticides can lead to activation or detoxification [52]. Thiono-type OP insecticides, such as malathion, are not AChE inhibitors and require metabolic activation to become strong irreversible inhibitors of AChE in vivo .…”

Section: Discussionmentioning

confidence: 99%

Characterization and Functional Analysis of Four Glutathione S-Transferases from the Migratory Locust, Locusta migratoria

et al. 2013

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Glutathione S-transferases (GSTs) play an important role in detoxification of xenobiotics in both prokaryotic and eukaryotic cells. In this study, four GSTs (LmGSTd1, LmGSTs5, LmGSTt1, and LmGSTu1) representing different classes were identified from the migratory locust, Locusta migratoria. These four proteins were heterologously expressed in Escherichia coli as soluble fusion proteins, purified by Ni2+-nitrilotriacetic acid agarose column and biochemically characterized. LmGSTd1, LmGSTs5, and LmGSTu1 showed high activities with 1-chloro-2, 4-dinitrobenzene (CDNB), detectable activity with p-nitro-benzyl chloride (p-NBC) and 1, 2-dichloro-4-nitrobenzene (DCNB), whereas LmGSTt1 showed high activity with p-NBC and detectable activity with CDNB. The optimal pH of the locust GSTs ranged between 7.0 to 9.0. Ethacrynic acid and reactive blue effectively inhibited all four GSTs. LmGSTs5 was most sensitive to heavy metals (Cu2+ and Cd2+). The maximum expression of the four GSTs was observed in Malpighian tubules and fat bodies as evaluated by western blot. The nymph mortalities after carbaryl treatment increased by 28 and 12% after LmGSTs5 and LmGSTu1 were silenced, respectively. The nymph mortalities after malathion and chlorpyrifos treatments increased by 26 and 18% after LmGSTs5 and LmGSTu1 were silenced, respectively. These results suggest that sigma GSTs in L. migratoria play a significant role in carbaryl detoxification, whereas some of other GSTs may also involve in the detoxification of carbaryl and chlorpyrifos.

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Section: Discussionmentioning

confidence: 99%

Characterization and Functional Analysis of Four Glutathione S-Transferases from the Migratory Locust, Locusta migratoria

et al. 2013

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“…This is the first MS evidence of phosphorylated GSH derivatives formed both in vivo and in vitro. Only the first steps have been taken in evaluating the toxicity of the phosphorylated conjugates , and other GSH-derived metabolites of OP metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…GSTs metabolize a variety of endogenous and exogenous toxicants by forming GSH conjugates with the compounds directly or their reactive intermediates – . The action of GSTs on OP pesticides can lead to activation or detoxification . GST with GSH dealkylates methyl or ethyl groups (e.g., methyl parathion and parathion) and dearylates diazinon and diazoxon – .…”

Section: Introductionmentioning

confidence: 99%

Glutathione S-Transferase Conjugation of Organophosphorus Pesticides Yields S-Phospho-, S-Aryl-, and S-Alkylglutathione Derivatives

Fujioka

Casida

2007

Chem. Res. Toxicol.

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Pesticide detoxification is a central feature of selective toxicity and safety evaluation. Two of the principal enzymes involved are GSH S-transferases (GSTs) and cytochrome P450s acting alone and together. More than 100 pesticides are organophosphorus (OP) compounds, but with few exceptions, their GSH conjugates have not been directly observed in vitro or in vivo. The major insecticides chlorpyrifos (CP) and diazinon are of particular interest as multifunctional substrates with diverse metabolites, while ClP(S)(OEt) 2 and the cotton defoliant tribufos are possible precursors of phosphorylated GSH conjugates. Formation of GSH conjugates by GST with GSH was studied in vitro with and without metabolic activation by human liver microsomes or P450 3A4 with NADPH. Metabolites were analyzed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). Five GSH conjugates were identified from CP and chlorpyrifos oxon (CPO), i.e., GSCP and GSCPO in which the 6-chloro substituent of CP and CPO, respectively, is displaced by GSH; S-(3,5,6-trichloropyridin-2-yl)glutathione; S-(3,5-dichloro-6-hydroxypyridin-2-yl)glutathione; and S-ethylglutathione. GST of a human liver microsomal preparation but not P450 3A4 with GSH metabolized CP to GSCP. With GST and GSH, diazinon and diazoxon gave S-(2-isopropyl-4-methylpyrimidin-6-yl)glutathione and ClP(S)(OEt) 2 yielded GSP(S)(OEt) 2. With microsomes, NADPH, GST, and GSH tribufos gave GSP(O)(SBu) 2. The liver of intraperitoneally treated mice contained GSCP from CP, GSP(S)(OEt) 2 from ClP(S)(OEt) 2, and GSP(O)(SBu) 2 from tribufos. GSP(S)(OEt) 2 and GSP(O)(SBu) 2 are the first S-phosphoglutathione metabolites observed in vitro and in vivo directly by LC-ESI-MS. Nine other OP pesticides gave only O-dealkylation in the GST/GSH system. GST-catalyzed metabolism joins P450s and hydrolases as important contributors to OP detoxification.

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Differential proteins revealed with proteomics in the brain tissue of Paralichthys olivaceus under the stress of methyl parathion

Huang

Chen

et al. 2008

Chinese Journal of Chromatography

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The proteins from the brain tissue of the fish Paralichtys olivaceus (PO) were separated by the optimized two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Approximately 650 protein spots in each gel were detected from the brain sample when applying 200 mg protein to a 2D-PAGE gel in the pH range of 3.0 - 10.0. The differential proteins from the PO brain were separated and identified by proteomic technologies and they were further selected as the potential protein markers to monitor the contamination levels of methyl parathion (MP). Compared with the control group, 17 differential proteins were obtained from the PO brain under the stress of MP at 3 mg/L. Among these spots, fourteen were up-regulated and three were down-regulated. Then these differential proteins were further identified by peptide mass fingerprint (PMF) and database search. The results showed that heat shock protein 70, glutathione S-transferase and cytochrome P450 were significantly found in those differential proteins. These proteins might have strong potential for monitoring the contamination levels of MP and searching for the toxicological mechanism, as well as to evaluate the degree of risk of human fatalities under the condition of MP pollution. The results indicated that the application of the multiple biomarkers has the advantages over that of the single biomarker for monitoring the levels of MP contamination in the flowing seawater.

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Oxidative Glutathione Conjugation and Its Novel Role in Activation of the Organophosphorus Insecticide Prothiofos

Cited by 5 publications

References 13 publications

Characterization and Functional Analysis of Four Glutathione S-Transferases from the Migratory Locust, Locusta migratoria

Characterization and Functional Analysis of Four Glutathione S-Transferases from the Migratory Locust, Locusta migratoria

Glutathione S-Transferase Conjugation of Organophosphorus Pesticides Yields S-Phospho-, S-Aryl-, and S-Alkylglutathione Derivatives

Differential proteins revealed with proteomics in the brain tissue of Paralichthys olivaceus under the stress of methyl parathion

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