Differential Proteome Profiling Analysis under Pesticide Stress by the Use of a Nano-UHPLC-MS/MS Untargeted Proteomic-Based Approach on a 3D-Developed Neurospheroid Model: Identification of Protein Interactions, Prognostic Biomarkers, and Potential Therapeutic Targets in Human IDH Mutant High-Grade Gliomas.

Autor:	Louati K; Laboratory of Pharmacology, Analytics and Galenic Drug Development- LR12ES09, Faculty of Pharmacy, University of Monastir, Road Avicenne, 5000 Monastir, Tunisia., Maalej A; Laboratory of Environmental Bioprocesses, Centre of Biotechnology of Sfax, Road of Sidi-Mansour, P.O. Box 1177, 3018 Sfax, Tunisia., Kolsi F; Department of Neurosurgery, 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, 3029 Sfax, 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, 3029 Sfax, Tunisia., Gdoura Y; Department of Neurosurgery, 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, 3029 Sfax, Tunisia., Borni M; Department of Neurosurgery, 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, 3029 Sfax, 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; Higher Institute of Applied Studies to Humanities of Tunis (ISEAHT), University of Tunis, 11 Road of Jebel Lakdhar, 1005 Tunis, Tunisia., Choura S; Laboratory of Environmental Bioprocesses, Centre of Biotechnology of Sfax, Road of Sidi-Mansour, P.O. Box 1177, 3018 Sfax, 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, 3018 Sfax, Tunisia., Mnif B; Department of Bacteriology, 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, 3029 Sfax, 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, 3029 Sfax, 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, 3029 Sfax, Tunisia., Boudawara MZ; Department of Neurosurgery, 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, 3029 Sfax, Tunisia., Safta F; Laboratory of Pharmacology, Analytics and Galenic Drug Development- LR12ES09, Faculty of Pharmacy, University of Monastir, Road Avicenne, 5000 Monastir, Tunisia.
Jazyk:	angličtina
Zdroj:	Journal of proteome research [J Proteome Res] 2023 Nov 03; Vol. 22 (11), pp. 3534-3558. Date of Electronic Publication: 2023 Aug 31.
DOI:	10.1021/acs.jproteome.3c00395
Abstrakt:	High-grade gliomas represent the most common group of infiltrative primary brain tumors in adults associated with high invasiveness, agressivity, and resistance to therapy, which highlights the need to develop potent drugs with novel mechanisms of action. The aim of this study is to reveal changes in proteome profiles under stressful conditions to identify prognostic biomarkers and altered apoptogenic pathways involved in the anticancer action of human isocitrate dehydrogenase (IDH) mutant high-grade gliomas. Our protocol consists first of a 3D in vitro developing neurospheroid model and then treatment by a pesticide mixture at relevant concentrations. Furthermore, we adopted an untargeted proteomic-based approach with high-resolution mass spectrometry for a comparative analysis of the differentially expressed proteins between treated and nontreated spheroids. Our analysis revealed that the majority of altered proteins were key members in glioma pathogenesis, implicated in the cellular metabolism, biological regulation, binding, and catalytic and structural activity and linked to many cascading regulatory pathways. Our finding revealed that grade-IV astrocytomas promote the downstream of the mitogen-activated-protein-kinases/extracellular-signal-regulated kinase (MAPK1/ERK2) pathway involving massive calcium influx. The gonadotrophin-releasing-hormone signaling enhances MAKP activity and may serve as a negative feedback compensating regulator. Thus, our study can pave the way for effective new therapeutic and diagnostic strategies to improve the overall survival.
Databáze:	MEDLINE
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