Abstract
Vanilloids, including capsaicin and eugenol, are ligands of transient receptor potential channel vanilloid subfamily member 1 (TRPV1). Prolonged treatment with vanilloids triggered the desensitization of TRPV1, leading to analgesic or antinociceptive effects. Caenorhabditis elegans (C. elegans) is a model organism expressing vanilloid receptor orthologs (e.g., OSM-9 and OCR-2) that are associated with behavioral and physiological processes, including sensory transduction. We have shown that capsaicin and eugenol hamper the nocifensive response to noxious heat in C. elegans. The objective of this study was to perform proteomics to identify proteins and pathways responsible for the induced phenotype and to identify capsaicin and eugenol targets using a thermal proteome profiling (TPP) strategy. The results indicated hierarchical differences following Reactome Pathway enrichment analyses between capsaicin- and eugenol-treated nematodes. However, both treated groups were associated mainly with signal transduction pathways, energy generation, biosynthesis and structural processes. Wnt signaling, a specific signal transduction pathway, is involved following treatment with both molecules. Wnt signaling pathway is noticeably associated with pain. The TPP results show that capsaicin and eugenol target OCR-2 but not OSM-9. Further protein–protein interaction (PPI) analyses showed other targets associated with enzymatic catalysis and calcium ion binding activity. The resulting data help to better understand the broad-spectrum pharmacological activity of vanilloids.
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Data Availability
The data that support the findings from this study are available from the corresponding author upon reasonable request. Proteome discoverer 2.4 and Metascape datasets can be found online at Mendeley Data (https://doi.org/10.17632/4kv68ds8p5.1).
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Acknowledgements
This project was funded by the National Sciences and Engineering Research Council of Canada (F. Beaudry discovery Grant Number RGPIN-2020-05228). Laboratory equipment was funded by the Canadian Foundation for Innovation (CFI) and the Fonds de Recherche du Québec (FRQ), the Government of Quebec (F. Beaudry CFI John R. Evans Leaders Grant Number 36706). F. Beaudry is the holder of the Canada Research Chair in metrology of bioactive molecule and target discovery (Grant Number CRC-2021-00160). This research was undertaken partly thanks to funding from the Canada Research Chairs Program. A Ph.D. scholarship was awarded to J. Ben Salem from the Fonds de recherche du Québec—Santé (FRQS).
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This study was supported by Natural Sciences and Engineering Research Council of Canada, RGPIN-2020-05228, Canadian Foundation for Innovation, 36706, Canada Research Chairs, CRC-2021-00160.
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BN: Planning and Execution of experiments, Writing - original draf. JBS: Execution of experiments, Writing - review & editing. FB: Conceptualization, Funding, Organisation, Writing - review & editing.
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Nkambeu, B., Salem, J.B. & Beaudry, F. Antinociceptive Activity of Vanilloids in Caenorhabditis elegans is Mediated by the Desensitization of the TRPV Channel OCR-2 and Specific Signal Transduction Pathways. Neurochem Res 48, 1900–1911 (2023). https://doi.org/10.1007/s11064-023-03876-1
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DOI: https://doi.org/10.1007/s11064-023-03876-1