A Proteomic Profile of Imidacloprid and its Active Metabolites Desnitro-Imidacloprid and Imidacloprid-Olefin in Human Neural Cells
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Girish Kumar, Sreehari
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Abstract
Neonicotinoids are a popular class of pesticides around the world and have been shown to bind both insect and mammalian nicotinic acetylcholine receptors (nAChRs). Imidacloprid (IMI), is amongst the most commonly used neonicotinoids in agriculture and domestic, non-industrial, applications but shows strong toxic effects in many organisms. In addition, the potential for toxicity from its two main metabolites desnitroimidacloprid (DN-IMI) and imidacloprid-olefin (IMI-olefin), are not yet defined despite recent evidence that they can bind to the mammalian nAChR. In this study, we used Lund Human Mesencephalic (LUHMES) cells, as a human cell line model of dopaminergic neurons to test the effects of IMI and its metabolites. Cells were treated with 50μM IMI, DN-IMI, and IMI-olefin for 48 hours, and then examined for proteomic change using liquid-chromatography electrospray ionization mass spectrometry (LC-ESI MS/MS). Bioinformatic analysis using Gene Ontology (GO) and enrichment analysis were performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and WikiPathways databases. Our results provide novel insight into convergent as well as differential molecular effects by IMI, DN-IMI, and IMI-olefin in neural cells. These studies begin to explore pathways of neonicotinoid neurotoxicity leading to neuro disease in exposed individuals.
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Mass Spectrometry Analysis, Imidacloprid, Imidacloprid-Olefin, Neonicotinoids, Proteomics, Des-nitro Imidacloprid