Review: Organophosphorus toxicants, in addition to inhibiting acetylcholinesterase activity, make covalent adducts on multiple proteins and promote protein crosslinking into high molecular weight aggregates

Lockridge, Oksana; Schopfer, Lawrence M.

doi:10.1016/j.cbi.2023.110460

Cited by 8 publications

(3 citation statements)

References 57 publications

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“…In addition, relatively high (or repeated) exposures to OP inhibitors are usually needed to surpass the threshold of approximately 50-75% AChE inhibition associated with mild to moderate OP poisoning [51]. By contrast, the structure-activity relationships of other proteins adducted by pesticides may differ from that for AChE [1,6,[8][9][10][11]18,26,27,52] and some could potentially be long-lasting and contribute to pesticide-induced ill health. Furthermore, as proposed herein, oxidatively-damaged proteins are generated after exposure to neurotoxicants at a concentration below the threshold required to induce neuronal death, and therefore this form of protein post-translational modification could potentially contribute to acute or chronic cellular damage.…”

Section: Differentiated Neurons Are More Vulnerable To Cholinergic To...mentioning

confidence: 99%

Differentiated Neurons Are More Vulnerable to Organophosphate and Carbamate Neurotoxicity than Undifferentiated Neurons Due to the Induction of Redox Stress and Accumulate Oxidatively-Damaged Proteins

et al. 2023

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Organophosphate (OP) and carbamate pesticides are toxic to pests through targeted inhibition of acetylcholinesterase (AChE). However, OPs and carbamates may be harmful to non-target species including humans and could induce developmental neurotoxicity if differentiated or differentiating neurons are particularly vulnerable to neurotoxicant exposures. Hence, this study compared the neurotoxicity of OPs, chlorpyrifos-oxon (CPO), and azamethiphos (AZO) and the carbamate pesticide, aldicarb, to undifferentiated versus differentiated SH-SY5Y neuroblastoma cells. OP and carbamate concentration-response curves for cell viability were undertaken using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and cellular bioenergetic capacity assessed via quantitation of cellular ATP levels. Concentration-response curves for inhibition of cellular AChE activity were also generated and the production of reactive oxygen species (ROSs) was monitored using a 2′,7′-dichlorofluorescein diacetate (DCFDA) assay. The OPs and aldicarb reduced cell viability, cellular ATP levels, and neurite outgrowth in a concentration-dependent fashion, from a threshold concentration of ≥10 µM. Neurotoxic potency was in the order AZO > CPO > aldicarb for undifferentiated cells but CPO > AZO > aldicarb for differentiated cells and this toxic potency of CPO reflected its more extensive induction of reactive oxygen species (ROSs) and generation of carbonylated proteins that were characterized by western blotting. Hence, the relative neurotoxicity of the OPs and aldicarb in part reflects non-cholinergic mechanisms that are likely to contribute to developmental neurotoxicity.

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Section: Differentiated Neurons Are More Vulnerable To Cholinergic To...mentioning

confidence: 99%

Differentiated Neurons Are More Vulnerable to Organophosphate and Carbamate Neurotoxicity than Undifferentiated Neurons Due to the Induction of Redox Stress and Accumulate Oxidatively-Damaged Proteins

et al. 2023

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“…21 One characteristic feature of this reaction is that OP adducts on BChE can be detected by mass spectrometry. [30][31][32] Additionally, BChE enzyme inhibited by OPs can be reactivated with numerous oximes. 20,21,[33][34][35] Frequently encountered nerve agents including V-type (VX, VM, VE, VG), G-type (soman, sarin, tabun, cyclosarin), and neurotoxic pesticides including aldicarb, carbofuran, and dichlorvos were depicted in Fig.…”

Section: Introductionmentioning

confidence: 99%

“…1A. 22,28,32,[36][37][38][39] Additionally, most common reactivators reported in the literature were summarized in Fig. 1B.…”

Section: Introductionmentioning

confidence: 99%

Optical imaging probes for selective detection of butyrylcholinesterase

Dirak,

Chan,

Kolemen

2024

J. Mater. Chem. B

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Probing the molecular mechanism of interaction between polystyrene nanoplastics and catalase by multispectroscopic techniques

Hu¹,

Xu²,

Cui³

et al. 2023

Chemico-Biological Interactions

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Review: Organophosphorus toxicants, in addition to inhibiting acetylcholinesterase activity, make covalent adducts on multiple proteins and promote protein crosslinking into high molecular weight aggregates

Cited by 8 publications

References 57 publications

Differentiated Neurons Are More Vulnerable to Organophosphate and Carbamate Neurotoxicity than Undifferentiated Neurons Due to the Induction of Redox Stress and Accumulate Oxidatively-Damaged Proteins

Differentiated Neurons Are More Vulnerable to Organophosphate and Carbamate Neurotoxicity than Undifferentiated Neurons Due to the Induction of Redox Stress and Accumulate Oxidatively-Damaged Proteins

Optical imaging probes for selective detection of butyrylcholinesterase

Probing the molecular mechanism of interaction between polystyrene nanoplastics and catalase by multispectroscopic techniques

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