A Shotgun Proteomic-Based Approach with a Q-Exactive Hybrid Quadrupole-Orbitrap High-Resolution Mass Spectrometer for the Assessment of Pesticide Mixture-Induced Neurotoxicity on a 3D-Developed Neurospheroid Model from Human Brain Meningiomas: Identification of Trityl-Post-Translational Modification.

Autor:	Louati K; Laboratory of Chemical, Galenic and Pharmacological Drug Development- LR12ES09, University of Monastir, Road Avicenne , 5000Monastir, Tunisia., Maalej A; Laboratory of Environmental Bioprocesses, Centre of Biotechnology of Sfax, Road of Sidi-Mansour, P.O. Box 1177 , 3018Sfax, Tunisia., Kolsi F; Department of Neurosurgery, Habib Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089Sfax, Tunisia.; Faculty of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia., Kallel R; Laboratory of Pathological Anatomy and Cytology, Habib Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089 Sfax, Tunisia.; Faculty of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia., Gdoura Y; Department of Neurosurgery, Habib Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089Sfax, Tunisia.; Faculty of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia., Borni M; Department of Neurosurgery, Habib Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089Sfax, Tunisia.; Faculty of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia., Hakim LS; Laboratory of Pathological Anatomy and Cytology, Habib Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089 Sfax, Tunisia., Zribi R; Faculty of Letters and Humanities, University of Sfax, Airport Road, Km 4.5, 3023 Sfax, Tunisia., Choura S; Laboratory of Environmental Bioprocesses, Centre of Biotechnology of Sfax, Road of Sidi-Mansour, P.O. Box 1177 , 3018Sfax, Tunisia., Sayadi S; Biotechnology Program, Center for Sustainable Development, College of Arts and Sciences, Qatar University, 2713 Doha, Qatar., Chamkha M; Laboratory of Environmental Bioprocesses, Centre of Biotechnology of Sfax, Road of Sidi-Mansour, P.O. Box 1177 , 3018Sfax, Tunisia., Mnif B; Department of Bacteriology, Habib Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089Sfax, Tunisia.; Faculty of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia., Khemakhem Z; Legal Medicine Department, Habib Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089 Sfax, Tunisia.; Faculty of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia., Boudawara TS; Laboratory of Pathological Anatomy and Cytology, Habib Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089 Sfax, Tunisia.; Faculty of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia., Boudawara MZ; Department of Neurosurgery, Habib Bourguiba University Hospital, Road El Ain km 1.5, Avenue of Ferdaous, 3089Sfax, Tunisia.; Faculty of Medicine, University of Sfax, Avenue of Majida Boulila, 3029Sfax, Tunisia., Bouraoui A; Laboratory of Chemical, Galenic and Pharmacological Drug Development- LR12ES09, University of Monastir, Road Avicenne , 5000Monastir, Tunisia., Kraiem J; Laboratory of Chemical, Galenic and Pharmacological Drug Development- LR12ES09, University of Monastir, Road Avicenne , 5000Monastir, Tunisia., Safta F; Laboratory of Chemical, Galenic and Pharmacological Drug Development- LR12ES09, University of Monastir, Road Avicenne , 5000Monastir, Tunisia.
Jazyk:	angličtina
Zdroj:	Journal of proteome research [J Proteome Res] 2024 Dec 06; Vol. 23 (12), pp. 5554-5576. Date of Electronic Publication: 2024 Nov 18.
DOI:	10.1021/acs.jproteome.4c00804
Abstrakt:	The widespread use of pesticides, particularly in combinations, has resulted in enhanced hazardous health effects. However, little is known about their molecular mechanism of interactions. The aim of this study was to assess the neurotoxicity effect of pesticides in mixtures by adopting a 3D in vitro developed neurospheroid model, followed by treatment by increased concentrations of pesticides for 24 h and analysis by a shotgun proteomic-based approach with high-resolution tandem mass spectrometry. Three proteins, namely, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH), α-enolase, and phosphoglycerate-kinase-1, were selected as key targets in the metabolic process. Only high doses of pesticides mitigated cell-density proliferation with the occurrence of apoptotic cells, which unlikely makes any neurological alterations in environmental regulatory exposures. The proteomic analysis showed that majority of altered proteins were implicated in cell metabolism. De novo peptide sequencing revealed ion losses and adduct formation, namely, a trityl-post-translational modification in the active site of 201-GAPDH protein. The study also highlights the plausible role of pyrethroids to be implicated in the deleterious effects of pesticides in a mixture. To the best of our knowledge, our finding is the first in toxicoproteomics to deeply elucidate pesticides' molecular interactions and their ability to adduct proteins as a pivotal role in the neurotoxicity mechanism.
Databáze:	MEDLINE
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