Involvement of the Prion Protein in the Protection of the Human Bronchial Epithelial Barrier Against Oxidative Stress

Amal Kouadri (1) , Mariam El Khatib (1) , Johanna Cormenier (1) , Sylvain Chauvet (1) , Waël Zeinyeh (1) , Micheline El Khoury (1) , Laurence Macari (1) , Pierre Richaud (2) , Christelle Coraux (3) , Isabelle Michaud-Soret (1) , Nadia Alfaidy (4) , Mohamed Benharouga (1)

1 BioMet - Biologie des Métaux
2 BIAM - Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB)
3 P3CELL - Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250
4 BCI - Biologie du Cancer et de l'Infection

AIM: Bronchial epithelium acts as a defensive barrier against inhaled pollutants and microorganisms. This barrier is often compromised in inflammatory airway diseases that are characterized by excessive oxidative stress responses, leading to bronchial epithelial shedding, barrier failure, and increased bronchial epithelium permeability. Among proteins expressed in the junctional barrier and participating to the regulation of the response to oxidative and to environmental stresses is the cellular prion protein (PrPC). However, the role of PrPC is still unknown in the bronchial epithelium. Herein, we investigated the cellular mechanisms by which PrPC protein participates into the junctional complexes formation, regulation, and oxidative protection in human bronchial epithelium. RESULTS: Both PrPC messenger RNA and mature protein were expressed in human epithelial bronchial cells. PrPC was localized in the apical domain and became lateral, at high degree of cell polarization, where it colocalized and interacted with adherens (E-cadherin/γ-catenin) and desmosomal (desmoglein/desmoplakin) junctional proteins. No interaction was detected with tight junction proteins. Disruption of such interactions induced the loss of the epithelial barrier. Moreover, we demonstrated that PrPC protection against copper-associated oxidative stress was involved in multiple processes, including the stability of adherens and desmosomal junctional proteins. INNOVATION: PrPC is a pivotal protein in the protection against oxidative stress that is associated with the degradation of adherens and desmosomal junctional proteins. CONCLUSION: Altogether, these results demonstrate that the loss of the integrity of the epithelial barrier by oxidative stress is attenuated by the activation of PrPC expression, where deregulation might be associated with respiratory diseases.

Mots clés: Prion protein; Bronchial epithelium; Oxidative stress; Copper; Junctional proteins

Domaines: Biologie cellulaire; Pneumologie et système respiratoire

Amal Kouadri, Mariam El Khatib, Johanna Cormenier, Sylvain Chauvet, Waël Zeinyeh, et al.. Involvement of the Prion Protein in the Protection of the Human Bronchial Epithelial Barrier Against Oxidative Stress. Antioxidants and Redox Signaling, 2019, 31 (1), pp.59-74. ⟨10.1089/ars.2018.7500⟩. ⟨hal-02092968⟩