Axis 1, Team 3 | Analysis of the impact of contaminants on plasma membrane and related consequences in cell responses

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We have previously demonstrated a role for membrane remodeling (changes in fluidity ; reorganization of lipid rafts) in the phenotypic responses induced upon hepatic cell exposure to benzo[a]pyrene (B[a]P; a well-known carcinogenic polycyclic aromatic hydrocarbon [PAH]) and ethanol, used alone or in combination. Regarding the effect of B[a]P, we have furthermore demonstrated a role for AhR and reactive oxygen species (ROS) in the lipid composition changes of lipid rafts. We will carry on this work by testing the effects of other PAHs as well as other contaminants with different modes of action. Membrane remodeling will be studied both in vitro in diverse hepatic cells (primary hepatocytes, WIF-B9 and HepaRG cell lines) notably thanks to our “Membrane & Stress” Plateau, and in vivo in zebrafish larvae using a fluorescence methodology recently adapted by our team. The consequences of such a remodeling will be tested on various cell responses (oxidative stress, energy metabolism [Seahorse technology], cell death, cell survival).

 

Confocal microscopy analysis of the ethanol-induced membrane remodeling in liver of Zebrafish larvae - 
 - © Irset - Institut de recherche en santé, environnement et travail - Rennes, Bretagne, France

Proteins located in plasma membrane may also be direct targets of contaminants, as previously evidenced by our team for the b2 adrenoceptor upon PAH exposure. These studies have therefore unveiled new early targets for environmental contaminants but a lot remains to be explored. By using in vitro cell models, we will study the interactions between our test environmental contaminants and GPCRs.