Dépôt numérique

Methylglyoxal and glyoxal affect the protein cargoes in neuronal-derived extracellular vesicles

Haddad, Mohamed; Perrotte, Morgane; ben Khedher, Mohamed Raâfet; Fulop, Tamas et Ramassamy, Charles . Methylglyoxal and glyoxal affect the protein cargoes in neuronal-derived extracellular vesicles In: International Society for Extracellular Vesicles (Annual Meeting ISEV 2020), 20-22 July 2020, virtuel.

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Introduction: Advanced glycation end-products (AGEs) and their receptor RAGEs are known to be involved in the pathogenesis of Alzheimer’s disease (AD). Methylglyoxal (MG) or glyoxal (GO) are the precursors of AGEs and particularly N-(1-carboxymethyl)-L-lysine (CML), the most abundant AGEs. MG induced tau hyperphosphorylation and causes hippocampal damage and memory impairment in mice. The aim of our study was to analyze the effects of MG and GO on the neuroprotective, neurotrophic factors, inflammatory and neurodegenerative markers in the human cell line SK-N-SH and their release into the neuronal derived-EVs.

Methods: Briefly, SK-N-SH cells were incubated in FBS free media with MG and GO (0.5 mM) for 24 hours. Neuronal derived-EVs (nEVs) from culture media were isolated as previously described (Haddad et al. 2019). nEVs were characterized by electronic microscopy, NTA and by Western Blot. Cellular and nEVs concentrations of BDNF, PRGN, NSE, APP, MMP9, ANGPTL-4, LCN2, PTX2, S100B, RAGE, DJ-1 and alpha synuclein were determined by a Luminex assay from R& D Systems, Inc.. Aβ1-40, Aβ1-42, pTau T181 and total tau levels were measured also with luminex assay from EMD Millipore Corp.

Results: We found that both AGEs precursors, at non toxic concentration, reduced the neuronal levels of NSE with no effect on BDNF, PTRX-2, LCN-2, DJ-1, on neurodegenerative markers and on CML. GO decreased the levels of PRGN, APP, ANGPL-4 while the expressions of MMP-9 and ANGPL-4 were, respectively lower and higher in the presence of MG. MG and GO greatly reduced the release of LCN-2 by neuronal cells in nEVs. BDNF and PRGN in nEVs were reduced in the presence of GO. Both MG and GO did not modify the release of NSE, APP, MMP9, AGNTL-4, PTX-2, DJ-1, Aβ, pTau and CML in nEVs.

Summary/Conclusion: Our data demonstrated that MG and GO differently affect the content of some protein cargoes in nEVs and suggest that targeting MG and GO may be a promising therapeutic strategy to prevent neurodegeneration.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique


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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 14 juill. 2021 15:40
Dernière modification: 14 juill. 2021 15:40
URI: https://espace.inrs.ca/id/eprint/11868

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