Titre
Protein pathway analysis to study development-dependent effects of acute and repeated trimethyltin (TMT) treatments in 3D rat brain cell cultures.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Schvartz, D.
Auteure/Auteur
González-Ruiz, V.
Auteure/Auteur
Walter, N.
Auteure/Auteur
Antinori, P.
Auteure/Auteur
Jeanneret, F.
Auteure/Auteur
Tonoli, D.
Auteure/Auteur
Boccard, J.
Auteure/Auteur
Zurich, M.G.
Auteure/Auteur
Rudaz, S.
Auteure/Auteur
Monnet-Tschudi, F.
Auteure/Auteur
Sandström, J.
Auteure/Auteur
Sanchez, J.C.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1879-3177
Statut éditorial
Publié
Date de publication
2019-10
Volume
60
Première page
281
Dernière page/numéro d’article
292
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Trimethyltin is an organometallic compound, described to be neurotoxic and to trigger neuroinflammation and oxidative stress. Previous studies associated TMT with the perturbation of mitochondrial function, or neurotransmission. However, the mechanisms of toxicity may differ depending on the duration of exposure and on the stage of maturation of brain cells. This study aim at elucidating whether the toxicity pathways triggered by a known neurotoxicant (TMT) differs depending on cell maturation stage or duration of exposure. To this end omics profiling of immature and differentiated 3D rat brain cell cultures exposed for 24 h or 10 days (10-d) to 0.5 and 1 μM of TMT was performed to better understand the underlying mechanisms of TMT associated toxicity. Proteomics identified 55 and 17 proteins affected by acute TMT treatment in immature and differentiated cultures respectively, while 10-day treatment altered 96 proteins in immature cultures versus 353 in differentiated. The results suggest different sensitivity to TMT depending on treatment duration and cell maturation. In accordance with known TMT mechanisms oxidative stress and neuroinflammation was observed after 10-d treatment at both maturation stages, whereas the neuroinflammatory process was more prominent in differentiated cultures than in the immature, no development-dependent difference could be detected for oxidative stress or synaptic neurodegeneration. Pathway analysis revealed that both vesicular trafficking and the synaptic machinery were strongly affected by 10-d TMT treatment in both maturation stages, as was GABAergic and glutamatergic neurotransmission. This study shows that omics approaches combined with pathway analysis constitutes an improved tool-set in elucidating toxicity mechanisms.
PID Serval
serval:BIB_71CF0C89DD43
PMID
Date de création
2019-06-24T06:35:42.342Z
Date de création dans IRIS
2025-05-21T04:07:44Z