A proteomic view of cellular responses of macrophages to copper when added as ion or as copper-polyacrylate complex - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Proteomics Année : 2021

A proteomic view of cellular responses of macrophages to copper when added as ion or as copper-polyacrylate complex

Résumé

Copper is an essential metal for life, but is toxic at high concentrations. In mammalian cells, two copper transporters are known, CTR1 and CTR2. In order to gain insights on the possible influence of the import pathway on cellular responses to copper, two copper challenges were compared: one with copper ion, which is likely to use preferentially CTR1, and one with a copper-polyacrylate complex, which will be internalized via the endosomal pathway and is likely to use preferentially CTR2. A model system consisting in the J774A1 mouse macrophage system, with a strong endosomal/lysosomal pathway, was used. In order to gain wide insights into the cellular responses to copper, a proteomic approach was used. The proteomic results were validated by targeted experiments, and showed differential effects of the import mode on cellular physiology parameters. While the mitochondrial transmembrane potential was kept constant, a depletion in the free glutahione content was observed with copper (ion and polylacrylate complex). Both copper-polyacrylate and polyacrylate induced perturbations in the cytoskeleton and in phagocytosis. Inflammatory responses were also differently altered by copper ion and copper-polyacrylate. Copper-polyacrylate also perturbed several metabolic enzymes. Lastly, enzymes were used as a test set to assess the predictive value of proteomics. SIGNIFICANCE: Proteomic profiling provides an in depth analysis of the alterations induced on cells by copper under two different exposure modes to this metal, namely as the free ion or as a complex with polyacrylate. The cellular responses were substantially different between the two exposure modes, although some cellular effects are shared, such as the depletion in free glutathione. Targeted experiments were used to confirm the proteomic results. Some metabolic enzymes showed altered activities after exposure to the copper-polyacrylate complex. The basal inflammatory responses were different for copper ion and for the copper-polyacrylate complex, while the two forms of copper inhibited lipopolysaccharide-induced inflammatory responses.
Fichier principal
Vignette du fichier
Cu ion paa final complete.pdf (1.69 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03223058 , version 1 (18-05-2021)

Licence

Paternité - Pas de modifications

Identifiants

Citer

Bastien Dalzon, Julie Devcic, Joanna Bons, Anaëlle Torres, Hélène Diemer, et al.. A proteomic view of cellular responses of macrophages to copper when added as ion or as copper-polyacrylate complex. Journal of Proteomics, 2021, 239, pp.104178. ⟨10.1016/j.jprot.2021.104178⟩. ⟨hal-03223058⟩
142 Consultations
75 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More